Reaxys Anonymous 20131108 024356 919

Query
Query Results Date
1. Query
224 reactions in 2013-11-08 02h:39m:04s (EST) Reaxys

N N H
Search as: Ignore stereo, No salts, No mixtures, No isotopes, No charges, No radicals
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HN O
HN O
HN
Rx-ID: 25854575 View in Reaxys 1/224 Yield 80.4 % Conditions & References A.A7.c :c) Preparation of intermediate 30; A solution of intermediate 29 (0.0448 mol) in CH3OH (150 ml) was hydrogenated at 75 0C under 90 atm of pressure with Pd/C 10 percent (1 g) as a catalyst. After uptake of H2 (3 equiv), the catalyst was filtered off and the filtrate was evaporated. The oily residue was triturated under diethyl ether, filtered off, washed, then dried (vacuum, 55 C).Yield: 9.3 g of intermediate 30 (80.4 percent). With hydrogen, palladium 10 on activated carbon in methanol, T= 75 C , p= 68404.6Torr Patent; JANSSEN PHARMACEUTICA N.V.; WO2007/90826; (2007); (A1) English View in Reaxys 80 % With palladium on activated charcoal, hydrogen in methanol, T= 75 C Bongartz, Jean-Pierre; Buntinx, Mieke; Coesemans, Erwin; Hermans, Bart; Wauwe, Jean Van; Lommen, Guy Van; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 21; (2008); p. 5819 - 5823 View in Reaxys
H N
O O
O O
Rx-ID: 27746688 View in Reaxys 2/224 Yield 100 % Conditions & References Ethyl 2-methyl-2-(4-piperidyl)propanoate; Ethyl 2-methyl-2-pyridin-4-yl-propanoate (1.50 g, 7.77 mmol) in ethanol (100 ml) and 5percent rhodium on alumina (150 mg, 0.075 mmol) were stirred under an atmosphere of hydrogen at a pressure of 4 bars and a temperature of 25 C. for 12 hours.The reaction mixture was filtered through Celite to remove the catalyst. The solvent was evaporated under reduced pressure to give ethyl 2-methyl-2-(4-piperidyl)propanoate as a black oil (quantitative reaction).1H NMR (300.073 MHz, DMSO-d6) 1.04 (6H, s), 1.17 (3H, t), 1.25-1.33 (2H, m), 1.48 (1H, d), 1.52-1.64 (2H, m), 1.80 (1H, s), 2.55-2.61 (2H, m), 3.09 (2H, d), 4.05 (2H, q) With hydrogen, 5 Rh/Al2O3 in ethanol, Time= 12h, T= 25 C , p= 3000.3Torr Patent; AstraZeneca AB; US2008/269288; (2008); (A1) English View in Reaxys
OH
N
N
HN OH
OH
HO
Rx-ID: 22977286 View in Reaxys 3/224 Yield 82 % Conditions & References 12 : 2-[(2-hydroxy-ethyl)-(2-piperidin-4-yl-ethyl)-amino]-ethanol 1.0 g activated ruthenium oxide is added to a solution of 57 g (0.27 mol) 2-[(2-hydroxy-ethyl)-(2-pyridin-4-yl-ethyl)amino]-ethanol (Chem. Abstr. 1960, 13129) in 700 ml methanol and hydrogenated for 16 h at 100 C. and 150 bar hydrogen pressure. It is filtered, concentrated by evaporation and chromatographed on silica gel. 47.9 g (82percent of theory) of the desired compound is eluted as an oil with methanol. With hydrogen, ruthenium(IV) oxide in methanol, Time= 16h, T= 100 C , p= 112511Torr
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Patent; Roche Diagnostics GmbH; US2003/236266; (2003); (A1) English View in Reaxys
OH OH HCl
OH OH
N H
Rx-ID: 23422035 View in Reaxys 4/224 Yield 80 % Conditions & References A.12.2A :A solution OF 4 N HCI in dioxane (5.06 mL) was added to a solution of the pyridine (1.41 g, 10.1 mmol) in MeOH (5 mL). The solution was stirred at room temperature for 1 hour, and solvent was removed under reduced pressure to give a white solid, 1.68 g (94percent). A mixture of the HCI salt of the pyridine (1.57 g, 8.94 MMMOL), platinum oxide (100 mg, 0.44 mmol), 1.0 N hydrochloric acid (1.4 mL) in ethanol (20 ML) was kept at 55 psi of hydrogen gas at room temperature for 7.5 hours. The solvent was then removed under reduced pressure to deliver 1. 67 g of a yellow oil (composition of sample: 80percent title compound, 20percent mono-ol based on 'H NMR). MS (APCI) (M+L)/ Z 145.9. With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, Time= 7.5h, T= 20 C , p= 2844.39Torr Patent; WARNER-LAMBERT COMPANY LLC; WO2005/26145; (2005); (A2) English View in Reaxys
HN O
N
O
HN
N NH NH
N NH
Rx-ID: 29194316 View in Reaxys 5/224 Yield 62% Conditions & References 83 :The mixture of 9-phenyl-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (150 mg, 0.4 mmol), con.HCl (0.6 mL) and Platinum (IV) oxide monohydrate (40 mg) in methanol (30 mL) was purged with 50 atm of hydrogen at 50 C. for 18 h. Then the mixture was filtered. The solvent was removed in vacuum to obtain a crude oil which was purified by prep-HPLC to give 9-phenyl-8-(piperidin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (95 mg, yield 62percent). 1H-NMR (400 MHz, DMSO-d6) (ppm): 1.24-1.41 (m, 1H), 1.49-1.59 (m, 1H), 1.69-1.78 (m, 2H), 1.98-2.01 (d, J=13.2 Hz, 1H), 2.67-2.86 (m, 2H), 3.22-3.31 (m, 3H), 4.18 (s, 1H), 7.05-7.08 (m, 3H), 7.14-7.21 (m, 2H), 7.24-7.28 (m, 2H), 7.31-7.33 (d, J=7.2 Hz, 1H), 7.52-7.56 (t, J=8.0 Hz, 1H), 8.19-8.24 (m, 1H), 8.54-8.56 (m, 1H), 12.30 (s, 1H); LC-MS (m/z) 347 (M+1)+. With hydrogenchloride, hydrogen, Adam's catalyst in methanol, water, Time= 18h, T= 50 C , p= 38002.6Torr Patent; LEAD THERAPEUTICS, INC.; US2010/35883; (2010); (A1) English View in Reaxys 62 % 83 :Example 839-Phenyl-8-(piperidin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-.pound./e]phthalazin-3(7H)-one[00645] The mixture of 9-phenyl-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-.pound./e]phthalazin-3(7H)-one (150 mg, 0.4 mmol), con.HCl (0.6 mL) and Platinum (IV) oxide monohydrate (40 mg) in methanol (30 mL) was purged with 50 atm of hydrogen at 50 C for 18 h. Then the mixture was filtered. The solvent was removed in vacuum to obtain a crude oil which was purified by prep-HPLC to give 9-phenyl-8- (piperidin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-.pound./e]phthalazin-3(7H)-one (95 mg, yield 62percent). ^-NMR (400 MHz, DMSO-i/6) (ppm): 1.24- 1.41 (m, 1H), 1.49-1.59 (m, 1H), 1.69-1.78(m, 2H), 1.98-2.01 (d, J = 13.2 Hz, 1H), 2.67-2.86 (m, 2H), 3.22-3.31 (m, 3H), 4.18 (s, 1H), 7.05-7.08 (m, 3H), 7.14-7.21 (m, 2H), 7.24-7.28 (m, 2H), 7.31-7.33 (d, J= 7.2 Hz, 1H), 7.52-7.56 (t, J= 8.0 Hz, 1H), 8.19-8.24 (m, 1H), 8.54-8.56 (m, 1H), 12.30 (s, 1H); LC-MS (m/z) 347 (M+l)+. With hydrogenchloride, hydrogen, Adam's catalyst in methanol, Time= 18h, T= 50 C , p= 38002.6Torr Patent; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHU, Daniel; WO2011/130661; (2011); (A1) English View in Reaxys
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H N
HO
HO
Rx-ID: 74795 View in Reaxys 6/224 Yield 95 % Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, Time= 48h, p= 2585.7Torr Egbertson, Melissa S.; Chang, Charles T.-C.; Duggan, Mark E.; Gould, Robert J.; Halczenko, Wasyl; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 16; (1994); p. 2537 - 2551 View in Reaxys 90 % With hydrogen, acetic acid, 10percent Pd/C, T= 20 C , p= 2585.81Torr He, Henry T.; Siahaan, Teruna J.; Song, Xiaoping; Organic Letters; vol. 4; nb. 4; (2002); p. 549 - 552 View in Reaxys 85 % With hydrogen, Rh on carbon in ethanol, Time= 24h, T= 60 C , p= 3102.89Torr , Catalytic hydrogenation Bruns, Robert F.; Cantrell, Buddy E.; Chaney, Michael O.; Clay, Michael P.; Gehlert, Donald R.; Hahn, Patric J.; Hunden, David C.; Johnson, Douglas W.; Ornstein, Paul L.; Schober, Douglas A.; Siegel, Miles G.; Zarrinmayeh, Hamideh; Zimmerman, Dennis M.; Van Abbema, Anne M.; Koppel, Gary A.; Tetrahedron; vol. 55; nb. 39; (1999); p. 11619 - 11639 View in Reaxys With water, acetic acid, platinum, Hydrogenation Schaefgen et al.; Journal of Polymer Science; vol. 40; (1959); p. 377,384 View in Reaxys Burtner; Brown; Journal of the American Chemical Society; vol. 69; (1947); p. 630,631 View in Reaxys With Rh/Al2O3 in methanol Bennani, Youssef L; Dwight, Wesley; Esbenshade, Timothy A; Faghih, Ramin; Fox, Gerard B; Gentles, Robert; Gopalakrishnan, Sujatha M; Hancock, Arthur A; Ireland, Lynne; Kang, Chae-Hee; Miller, Thomas R; Phelan, Kathleen; Bioorganic and Medicinal Chemistry Letters; vol. 12; nb. 15; (2002); p. 2031 - 2034 View in Reaxys 71.a : a a 3-(4-piperidinyl)propanol 3-(4-piperidinyl)propanol was prepared by hydrogenation of 3-(4-pyridyl)propanol in acetic acid in the presence of Pd/ C according to the method described in J. Org. Chem., 1962, 27, 2966-2967. With palladium monocarbide in acetic acid Patent; SANOFI; US5714497; (1998); (A1) English View in Reaxys 3 :Example 3 1-Methyl-4-Piperidinepropanol An Argonaut reaction vessel was charged with 4-pyridinepropanol (500.0 mg, 3.49 mmol) and 5percent Rh/C (62percent wet, 300.0 mg) in water (4.00 g). The resultant slurry was stirred at 500 RPM and the unit was pressurized with 300 psi of hydrogen. The resultant mixture was heated at 50 C. for about 4-4.5 h, during which time the hydrogen uptake ceased. The resultant mixture was then cooled to room temperature and a 37percent formaldehyde solution (340.0 mg, 4.19 mmol) was added in a single portion. The Argonaut vessel was sealed and the resultant slurry was stirred at 500 RPM, the unit was repressurized with 300 psi of hydrogen, and heated to 50 C. Hydrogen uptake ceased in about 1.2-1.5 h to yield the title compound, which was used in the next step without further purification or isolation. HPLC-MS analysis of an aliquot showed only C9H19NO
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MS: (Cl): m/z 158 (M++1) With hydrogen, 5 rhodium-on-charcoal in water, T= 50 C , p= 15514.9Torr Patent; Cesco-Cancian, Sergio; Chen, Hongfeng; Grimm, Jeffrey S.; Mani, Neelakandha S.; Mapes, Christopher M.; Palmer, David C.; Pippel, Daniel J.; Sorgi, Kirk L.; Xiao, Tong; US2010/4450; (2010); (A1) English View in Reaxys
H N
O O
O O
Rx-ID: 8548403 View in Reaxys 7/224 Yield 94 % Conditions & References With platinum(IV) oxide, hydrogen in acetic acid, Time= 0.333333h, T= 80 C , p= 6205.94Torr , Microwave irradiation Piras, Leonarda; Taddei, Maurizio; Genesio, Eva; Ghiron, Chiara; Synlett; nb. 8; (2008); p. 1125 - 1128 View in Reaxys 88 % 11 With hydrogen, platinum(IV) oxide, Time= 18.5h, p= 3102.97Torr Patent; THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS; WO2008/134474; (2008); (A2) English View in Reaxys 58 % 10A Stage 1: With hydrogenchloride, hydrogen, palladium on activated charcoal in ethanol, water, Time= 48h, T= 20 C , pH= 2 Stage 2: With sodium hydroxide, water in ethyl acetate, pH= 13 Patent; BAYER HEALTHCARE AG; WO2005/68472; (2005); (A1) German View in Reaxys 58 % 4A Stage 1: With hydrogenchloride, hydrogen, palladium on carbon in ethanol, water, Time= 48h, T= 20 C , p= 2250.23Torr , pH= 2 Stage 2: With sodium hydroxide in water, ethyl acetate, pH= 13 Patent; BAYER HEALTHCARE AG; WO2005/77907; (2005); (A1) German View in Reaxys 5g With hydrogen, aluminum oxide in methanol, water, Time= 20h, p= 2660Torr , Catalytic hydrogenation Carpinelli; Colombo; Fazio; Kienle, M. Galli; Magni; Matarrese; Moresco; Simonelli; Soloviev; Todde; Kienle, M. Galli; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 43; nb. 4; (2000); p. 359 - 374 View in Reaxys With hydrogen, acetic acid, platinum(IV) oxide Islam, Imadul; Bryant, Judi; May, Karen; Mohan, Raju; Yuan, Shendong; Kent, Lorraine; Morser, John; Zhao, Lei; Vergona, Ron; White, Kathy; Adler, Marc; et al.; Bioorganic & Medicinal Chemistry Letters; vol. 17; nb. 5; (2007); p. 1349 - 1354 View in Reaxys 4 : EXAMPLE 4 STR27 EXAMPLE 4 STR27 Ethyl-4-pyridylacetate (5 g) is dissolved in ethanol (30 mL), treated with platinum oxide catalyst (30 mg) and hydrogenated on a Parr apparatus for 4 hr. The catalyst is filtered off and the ethyl-4-piperidinylacetate is isolated by removal of the solvent under vacuum.
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in ethanol Patent; Neurogen Corporation; US6084098; (2000); (A1) English View in Reaxys 7.a : EXAMPLE 7 a) 16.5 g (0.1 mol) Ethyl 4-pyridylacetate, 8.4 mL (0.1 mol) 12N hydrochloric acid and 2.5 g platinum oxide were dissolved in absolute ethanol and hydrogenated at 40 psi hydrogen on a Parr shaker. After 1 hour, the contents of the vessel were filtered and concentrated in vacuo yielding 27.79 g of ethyl 4-piperidinylacetate. With hydrogenchloride, hydrogen in ethanol Patent; Sterling Winthrop Inc.; US5242924; (1993); (A1) English View in Reaxys 13.a : EXAMPLE 13 a) 16.5 g (0.1 mol) Ethyl 4-pyridylacetate, 8.4 mL (0.1 mol) 12 N hydrochloric acid and 2.5 g platinum oxide were dissolved in absolute ethanol and hydrogenated at 40 psi hydrogen on a Parr shaker. After 1 hour, the contents of the vessel were filtered and concentrated in vacuo yielding 27.79 g of ethyl 4-piperidinylacetate. With hydrogenchloride, hydrogen in ethanol Patent; Sterling Winthrop Inc.; US5364865; (1994); (A1) English View in Reaxys 21.A : PREPARATIVE EXAMPLE 21; Step A [1989] Commercially available Ethyl 4-Pyridyl Acetate (4.5 g; 27.2 mmol), EtOH (70 ml) and 10percent Palladium on Charcoal (catalytic) was shaken under 55 psi hydrogen at room temperature for 94 hrs. The mixture was filtered through Celite and the cake was washed with (4.x.40 ml) of EtOH. The filtrate was concentrated and purified by flash silica column chromatography eluting with 3percent (10percent NH4OH:MeOH)/CH2Cl2. With ethanol, hydrogen, palladium 10 on activated carbon, Time= 94h, T= 20 C , p= 2844.39Torr Patent; Schering Corporation; US2004/122018; (2004); (A1) English View in Reaxys 18 :Ethyl 4-pyridyl acetate (4.5g, 27.24mmoles) is placed in a 500mL Parr bottle and dissolved in anhydrous EtOH (70mL). To the bottle is added 10percent Palladium on charcoal (1 0 g). The bottle is put on a hydrogenator and the contents shaken under 55 psi hydrogen pressure at 25C for 94h. The mixture is filtered through Celite.(R). and washed with 4x40mL anhydrous EtOH. The filtrate is rotovapped down and the residue chromatographed on silica gel using 3percent (10percent conc. NH4OH in methanol)dichloromethane as the eluant to give 2 944g of the title compound. With hydrogen, palladium 10 on activated carbon in ethanol, Time= 94h, T= 25 C , p= 2844.39Torr Patent; Schering Corporation; Pharmacopeia Drug Discovery, Inc.; EP1140909; (2005); (B1) English View in Reaxys With hydrogenchloride, platinum(IV) oxide, hydrogen in water, p= 2585.81Torr , Inert atmosphere, Autoclave Monovich, Lauren G.; Tommasi, Ruben A.; Fujimoto, Roger A.; Blancuzzi, Vincent; Clark, Kirk; Cornell, Wendy D.; Doti, Robert; Doughty, John; Fang, James; Farley, David; Fitt, John; Ganu, Vishwas; Goldberg, Ronald; Goldstein, Robert; Lavoie, Stacey; Kulathila, Raviraj; Macchia, William; Parker, David T.; Melton, Richard; O'Byrne, Elizabeth; Pastor, Gary; Pellas, Theodore; Quadros, Elizabeth; Reel, Noela; Roland, Dennis M.; Sakane, Yumi; Singh, Hem; Skiles, Jerry; Somers, Joseph; Toscano, Karen; Wigg, Andrew; Zhou, Siyuan; Zhu, Lijuan; Shieh, Wen-Chung; Xue, Song; McQuire, Leslie W.; Journal of Medicinal Chemistry; vol. 52; nb. 11; (2009); p. 3523 - 3538 View in Reaxys
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NH
NH
NH
Rx-ID: 30989374 View in Reaxys 8/224 Yield 73 % Conditions & References 8 :3-(Pyridin-4-ylmethyl)-1H-indole (5.00 g, 24.0 mmol) and acetic acid (25 mL) were added to platinum(IV) oxide (1.00 g, 4.40 mmol, Johnson Matthey) in a 250 mL stainless steel pressure bottle and stirred for about 2 hr under about 30 psi hydrogen at ambient temperature. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved with EtOAc and then washed with saturated aqueous Na2CO3. The organic layer became turbid. A small amount of MeOH was added to form a clear solution. The organic layer was washed with 2 N aqueous NaOH and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting solid was triturated with Et2O and then dried to give 3-(piperidin-4-ylmethyl)-1H-indole (4.35 g, 73percent yield): LC/MS (Table 1, Method a) Rt=1.51 min; MS m/z: 215.12 (M+H)+. Stage 1: With hydrogen, acetic acid, platinum(IV) oxide, Time= 2h, T= 20 C , p= 1551.49Torr Stage 2: With sodium carbonate in water, ethyl acetate Patent; ABBOTT LABORATORIES; US2011/152243; (2011); (A1) English View in Reaxys
H N
O O
O O
Cl
Rx-ID: 5317136 View in Reaxys 9/224 Yield Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, Time= 16h, T= 20 C , Catalytic hydrogenation Brundish, Derek; Bull, Alice; Donovan, Vera; Fullerton, Joseph D.; Garman, Sheila M.; Hayler, Judy F.; Janus, Diana; Kane, Peter D.; McDonnell, Mark; Smith, Garrick P.; Wakeford, Robert; Walker, Clive V.; Ambler, John; Butler, Keith; Talbot, Mark D.; Allen, Mark C.; Howarth, Graham; Hoyle, William; Kane, Peter D.; Journal of Medicinal Chemistry; vol. 42; nb. 22; (1999); p. 4584 - 4603 View in Reaxys 124 : Reference Example 124: Ethyl (piperidin-4-yl) acetate hydrochloride Ethyl (pyridin-4-yl)acetate (50.00 g) is dissolved in acetic acid (500 ml), thereto is added platinum oxide (3.44 g) and the mixture is shaken under 55 psi hydrogen atmosphere at room temperature for 20 hours. The insoluble materials are removed by filtration and the filtrate is concentrated under reduced pressure. The resulting residue is dissolved in dioxane (200 ml), thereto is added 4 N hydrogen chloride-dioxane (400 ml), and then the mixture is evaporated to remove the solvent under reduced pressure. The resulting residue is suspended in diethyl ether-diisopropyl ether, and the precipitates are collected by filtration, washed with diisopropyl ether, and then dried to give the title compound (61.80 g). APCI-MS M/Z:17-2[M+H]+. Stage 1: With hydrogen, acetic acid, platinum(IV) oxide, Time= 20h, T= 20 C , p= 2844.39Torr Stage 2: With hydrogenchloride in 1,4-dioxane Patent; Tanabe Seiyaku Co., Ltd.; EP1489078; (2004); (A1) English View in Reaxys 14 : Reference Example 14: Reference Example 14: Ethyl piperidin-4-ylacetate hydrochloride Ethyl (pyridin-4-yl)acetate (50.00 g) is dissolved in acetic acid (500 ml), and thereto is added platinum oxide (3.44 g). The mixture is shaken at room temperature for 20 hours under 55 psi hydrogen atmosphere. The insoluble materials are removed by filtration and the filtrate is concentrated under reduced pressure. The resulting residue is dissolved in dioxane (200 ml), and thereto is added 4 N hydrogen chloride/dioxane (400 ml). The mixture is then evaporated to remove the solvent under reduced pressure.
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The resulting residue is suspended in diethyl ether/diisopropyl ether, and the precipitates are collected by filtration. The resultant is washed with diisopropyl ether, and dried to give the title compound (61.80 g). APCI-MS M/Z:172[M+H]+. Stage 1: With hydrogen, acetic acid, platinum(IV) oxide, Time= 20h, T= 20 C , p= 2844.39Torr Stage 2: With hydrogenchloride in 1,4-dioxane Patent; TANABE SEIYAKU CO., LTD.; EP1582521; (2005); (A1) English View in Reaxys 1.C.1 :To a solution of ethyl 4-pyridylacetate (0.121 mol) in EtOH (100 mL) is added concentrated hydrochloric acid (11 mL), followed by the addition of platinum oxide (8.8 mmol). The resulting mixture is hydrogenated under hydrogen atmosphere (50 psi) till no more hydrogen absorption occurs. The catalyst is filtered off and washed with EtOH (20 mL x 2). The filtrate is concentrated to dryness in vacuo to give the title compound as the hydrochloric acid salt. With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, water, p= 2585.81Torr Patent; NEUROGEN CORPORATION; WO2007/16496; (2007); (A2) English View in Reaxys
H N
Rx-ID: 1557544 View in Reaxys 10/224 Yield 99 % Conditions & References With hydrogen, rhodium on alumina Meyers, A. I.; Shawe, Thomas T.; Gottlieb, Levi; Tetrahedron Letters; vol. 33; nb. 7; (1992); p. 867 - 870 View in Reaxys 86 % With hydrogen, acetic acid, Rh/Al2O3, [RhCl(2:2-cycloocta-1,5-diene)]2 in ethanol, Time= 24h, T= 50 C , p= 76000.1Torr Hayashi, Tamio; Sawamura, Masaya; Ito, Yoshihiko; Tetrahedron; vol. 48; nb. 11; (1992); p. 1999 - 2012 View in Reaxys 80.5 % With hydrogen, platinum(IV) oxide in ethanol, chloroform, Time= 48h, p= 2585.81Torr , Hydrogenation Chambournier; Gawley; Organic letters; vol. 2; nb. 11; (2000); p. 1561 - 1564 View in Reaxys 80.5 % With hydrogen, platinum(IV) oxide in ethanol, chloroform, Time= 48h, p= 2585.81Torr Chambournier; Gawley; Low; Organic letters; vol. 1; nb. 4; (1999); p. 653 - 655 View in Reaxys Reaction Steps: 2 1: HCl, gas / ethanol; diethyl ether / 1 h 2: 81.5 percent / H2 / PtO2 / ethanol / 24 h / 2280 Torr With hydrogenchloride, hydrogen, platinum(IV) oxide in diethyl ether, ethanol Goessinger,E.; Monatshefte fuer Chemie; vol. 113; (1982); p. 339 View in Reaxys Reaction Steps: 2 1: 2) 6 N HCl / diethyl ether; toluene / 14 h / Heating 2: 1) tert-butyl-pyridine, aq. NaOH; 2) Ru(OH)3, LiOH*H2O, 10 percent HCl / 1) Raney-nickel, aluminum / 1) tert-butyl alcohol, 60-70 deg C, 1 h; 2) H2O, 4053 kPa, 80-120 deg C, With hydrogenchloride, ruthenium trihydroxide, lithium hydroxide, sodium hydroxide, nickel, aluminium in diethyl ether, toluene
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Ogawa, Keiichiro; Takeuchi, Yoshito; Suzuki, Hiroshi; Nomura, Yujiro; Journal of the American Chemical Society; vol. 106; nb. 4; (1984); p. 831 - 840 View in Reaxys
H N
Rx-ID: 23513558 View in Reaxys 11/224 Yield 43.9 % Conditions & References 2.47.b :2.47.b 4-piperidin-1-ylmethyl-piperidine A solution of 106 g (0.6 mol) of 4-piperidin-1-ylmethyl-pyridine in 1.0 L glacial acetic acid is combined with 7 g platinum dioxide and shaken in the autoclave at ambient temperature and 3 bar hydrogen. After the catalyst has been suction filtered the solvent is eliminated using the rotary evaporator. The crude product is further reacted without purification. Yield: 48 g (43.9percent of theory). With hydrogen, platinum(IV) oxide in hydrogen, acetic acid, T= 20 C , p= 2250.23Torr Patent; Boehringer Ingelheim International GmbH; US2004/242572; (2004); (A1) English View in Reaxys
N
O HN
Rx-ID: 25680659 View in Reaxys 12/224 Yield 98 % Conditions & References 3.32 : 3.32 4-(2-Ethoxyethyl)piperidine (56NK129) 3.32 4-(2-Ethoxyethyl)piperidine (56NK129) 4-(2-Ethoxyethyl)pyridine (0.151 g, 1.0 mmol) was dissolved in EtOH (4 ml) and acetic acid (0.5 ml) and the flask was evacuated, flooded with hydrogen and this procedure was repeated twice. Platinium oxide (0.040 g) was added and the reaction was stirred vigorously at r.t. for 18 h. The reaction mixture was filtered through Celite eluding with EtOAc and the solute concentrated in vacuo. Ether (20 ml) was added and the reaction concentrated in vacuo. Sodium hydroxide (2 ml, 2 M) was added and the product was extracted into ether (2*20 ml). The organic phases were dried (K2CO3), filtered and carefully concentrated in vacuo to give the crude title compound (56NK129) as a yellow oil (0.154 g, 98percent). 1H NMR (CDCl ) 3.45 (m, 4H), 3.03 (m, 2H), 2.58 (m, 2H), 1.76 (br. S, 1H), 1.66 (m, 2H), 1.51 (m, 3H), 1.18 (t, J=7.5 3 Hz, 3H), 1.11 (m, 2H); HPLC-MS (ammonium acetate) [M+H]+=158.2 (calc. 158.2). Stage 1: With hydrogen, acetic acid, platinum(IV) oxide in ethanol, Time= 18h, T= 20 C Stage 2: With sodium hydroxide in water Patent; Kelly, Nicholas Michael; Koch, Kristian Norup; Tolf, Bo-Ragnar; US2004/67931; (2004); (A1) English View in Reaxys
OH
N H 2 Cl O
OH
N H 2 Cl O
NH 2 racemate
HN
NH 2 racemate
Rx-ID: 27873873 View in Reaxys 13/224
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Yield 88.2 %
Conditions & References (+/-)-f/7reo-2-Amino-3-hydroxy-3-(pyridin-4-yl)-1 -(pyrrolidin-1 -yl)propan-1- one dihydrochloride Compound 22 (500 mg, 1.61 mmol) was stirred in AcOH (10 ml_) with PtO2 hydrate typical (Pt content 79-84percent, 100 mg) under hydrogen at atmospheric pressure for 24 h at RT. After filtration on Celite.(R). 545, the filtrate was evaporated and the residue was dried under vacuum to give a beige solid (450 mg, 88.2 percent yield). The crude product was stirred in <n="30"/>Docket 18175 PCT (AP)MeOH (50 ml_) with Amberlite (Cl-) IRA-400 (9 ml_, 12.7 mmol washed beforehand by NaOH 0.5 N then water and MeOH) at RT for 15 min. The mixture was filtered off, the filtrate was evaporated and the free base form was purified by column chromatography (SiO2, CH2CI2:MeOH:20 percent NH3 in H2O = 70:30:8) to give (+/-)-tf7reo-2-amino-3-hydroxy-3-(piperidin-4-yl)-1- (pyrrolidin-1-yl)propan-1-one TTA 08144A (226 mg, 58percent yield). HCI Treatment in MeOH gave (+/-)-f/7reo-2-amino-3-hydroxy-3-(piperidin-4-yl)-1- (pyrrolidin-1-yl)propan-1one dihydrochloride Compound 302 (190 mg, 28 percent yield) as a white solid.2.HCI (+/-)-threoCompound 302MW: 314.25; Yield: 28.0 percent; White Solid; Mp (0C): 197.5Rf : 0.20 (CH2CI2:MeOH:20 percent NH3 in H2O = 70:30:8, free base). 1 H-NMR (CD3OD, ): 1.57-2.00 (m, 9H, 4xCH2
CH), 2.94-3.08 (m, 2H, CH&2-N),
3.46-3.77 (m, 7H, 3xCH2-N, CH-
N), 4.33 (s, 1 H, CH-O).13C-NMR (CD3OD, ): 22.5, 23.4, 24.1 , 24.7, 35.2, 42.2, 42.5, 45.4, 45.5,52.0, 69.8, 164.6.MSESI m/z (percent rel. Int.): 242.2 ([MH]+, 45), 129.1 (100). HPLC: Method A, detection UV 214 nm, RT = 0.70 min, peak area 98.0 percent. With hydrogen, platinum(IV) oxide in acetic acid, Time= 24h, T= 20 C Patent; ALLERGAN, INC.; WO2008/109285; (2008); (A1) English View in Reaxys
N HN O N NH NH N O N HN N NH
Rx-ID: 29068803 View in Reaxys 14/224 Yield 16 % Conditions & References 15 :A mixture of 8,9-di(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (120 mg, 0.35 mmol), platinum (IV) oxide (60 mg) and concentrate hydrochloric acid (0.3 mL) in methanol (20 mL) was stirred at 50 C. under 20 atm of hydrogen. The mixture was filtered out and the filtrate was concentrated to give crude product. The crude product was purified by prep-HPLC to give 9-(piperidin-4-yl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)one (17.6 mg, yield: 16percent) as a light yellow solid. 1H-NMR (400 MHz, CD3OD) 1.25-1.39 (m, 1H), 1.40-1.52 (m, 1H), 1.60-1.70 (m, 1H), 1.75-1.84 (m, 1H), 1.89-1.98 (m, 1H), 2.50-2.57 (m, 1H), 2.60-2.66 (m, 1H), 3.09-3.21 (m, 2H), 3.34-3.37 (dd, J1=8 Hz, J2=2.4 Hz, 1H), 4.24 (d, J=2 Hz, 1H), 7.02-7.04 (dd, J1=8 Hz, J2=0.8 Hz, 1H), 7.09-7.11 (dd, J1=4.8 Hz, J2=1.2 Hz, 2H), 7.41-7.43 (dd, J1=7.6 Hz, J2=0.8 Hz, 1H), 7.50-7.54 (t, J=8 Hz, 1H), 8.30-8.32 (dd, J1=4.4 Hz, J2=1.6 Hz, 2H); LC-MS (ESI) m/z: 348(M+1)+ With hydrogenchloride, hydrogen, Adam's catalyst in methanol, T= 50 C , p= 15201Torr Patent; LEAD THERAPEUTICS, INC.; US2010/35883; (2010); (A1) English View in Reaxys 16 % 15 :Example 159-(Piperidin-4-yl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-<ie]phthalazin-3(7H)-one[00518] A mixture of 8,9-di(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-i/e]phthalazin-3(7H)-one (120 mg, 0.35 mmol), platinum (IV) oxide (60 mg) and concentrate hydrochloric acid (0.3 mL) in methanol (20 mL) was stirred at 50C under 20 atm of hydrogen. The mixture was filtered out and the filtrate was concentrated to give crude product. The crude product was purified by prep-HPLC to give 9-(piperidin-4- yl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-<ie]phthalazin-3(7H)-one (17.6 mg, yield: 16percent) as a light yellow solid. ^-NMR (400 MHz, CD3OD) 1.25- 1.39 (m, 1H), 1.40-1.52 (m, 1H), 1.60-1.70 (m, 1H), 1.75-1.84 (m, 1H), 1.89-1.98 (m, 1),2.50-2.57 (m, 1H), 2.60-2.66 (m, 1H), 3.09-3.21 (m, 2H), 3.34-3.37 (dd, J, = 8 Hz, J2 = 2.4 Hz, 1H), 4.24 (d, J= 2 Hz , 1H), 7.02-7.04 (dd, J, = 8 Hz, J2 = 0.8 Hz, 1H), 7.09-7.1 1 (dd, J, = 4.8 Hz, J2= 1.2 Hz, 2H), 7.41-7.43 (dd, J, = 7.6 Hz, J2 = 0.8 Hz, 1H), 7.50-7.54 (t, J= 8 Hz, 1H), 8.30-8.32 (dd, J = 4.4 Hz, J2 = 1.6 Hz, 2H); LC-MS (ESI) m/z: 348(M+1)+. With hydrogenchloride, platinum(IV) oxide in methanol, T= 50 C , p= 15201Torr Patent; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHU, Daniel; WO2011/130661; (2011); (A1) English View in Reaxys
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O N
O N HCl
N H
Rx-ID: 35348517 View in Reaxys 15/224 Yield 100% Conditions & References 12.C : C. [1,1-Biphenyl]-4-yl-(3-(piperidin-4-yl)azetidin-1-yl)methanone, 12d Compound 12c and 10percent palladium on carbon were combined in a 1:5 mixture of 1N aqueous HCl and ethanol in a Parr pressure bottle. _;The mixture was purged with N2 and then shaken under a 55 psi H2 atmosphere at 20 C. _;When the reaction was complete, the catalyst was removed by filtration through a diatomaceous earth pad. _;The filtrate was concentrated and lyophilized to provide compound 12d in quantitative yield as the hydrochloride salt. With hydrogenchloride, palladium 10 on activated carbon, hydrogen in ethanol, water, T= 20 C , p= 2844.39Torr , Inert atmosphere Patent; Connolly, Peter J.; Bian, Haiyan; Li, Xun; Liu, Li; Macielag, Mark J.; McDonnell, Mark E.; US2013/102584; (2013); (A1) English View in Reaxys
N
O O
O O
HCl NH
Rx-ID: 23509841 View in Reaxys 16/224 Yield Conditions & References 74.b :0.115 g of methyl 2-methyl-2-pyridin-4-ylpropionate (CAS 79757-27-0) are dissolved in 5 ml of methanol in an autoclave. The solution is admixed with 0.35 ml of 1.2M HCI in methanol and 0.012 g of platinum (IV) oxide, and the reaction mixture is hydrogenated at 4 bar and 23 over 46 hours. The catalyst is filtered off through Hyflo and the filtrate is concentrated by evaporation. The title compound is obtained as a light brown solid. Rf 0. 05 (200: 20: 1 dichloromethane-methanol-25percent conc. ammonia). With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 46h, T= 23 C , p= 3000.3Torr Patent; SPEEDEL EXPERIMENTA AG; WO2005/70871; (2005); (A2) English View in Reaxys 122.b :0.115 g of methyl 2-methyl-2-pyridin-4-ylpropionate (CAS 79757-27-0) is dissolved in an autoclave in 5 ml of methanol. The solution is admixed with 0.35 mi of 1.2M HCI in methanol and 0.012 g of platinum (IV) oxide, and the reaction mixture is hydrogenated at 4 bar and 23 over 46 hours. The catalyst is filtered off through Hyflo and the filtrate is concentrated by evaporation. The title compound is obtained as a light brown solid. Rf 0. 05 (200 : 20: 1 dichloromethane-methanol-25percent conc. ammonia). With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 46h, T= 23 C , p= 3000.3Torr Patent; SPEEDEL EXPERIMENTA AG; WO2005/70877; (2005); (A1) English View in Reaxys a :a) Methyl 2-methyl-2-piperidin-4-ylpropionate hydrochloride; 0. 115 g of methyl 2-methyl-2-pyridin-4-ylpropionate [79757-27-0] are dissolved in 5 mi of methanol in an autoclave. The solution is admixed with 0. 35 ml of 1. 2M HCl in methanol and 0. 012 g of platinum (IV) oxide and the reaction mixture is hydrogenated at 4 bar and 23C over 46 hours. The catalyst is filtered off through Hyflo and the filtrate is concentrated by evaporation. The title compound is obtained as a tight brown residue. Rf = 0. 05 (200 : 20 : 1 dichloromethane-methanol-25percent conc. ammonia) With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 46h, T= 23 C , p= 3000.3Torr Patent; SPEEDEL EXPERIMENTA AG; WO2005/90304; (2005); (A1) English
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View in Reaxys
H N
O OH
O OH
Rx-ID: 3947329 View in Reaxys 17/224 Yield 87 % Conditions & References With hydrogen, platinum(IV) oxide in water, acetic acid, Time= 72h, p= 2844.3Torr Egbertson, Melissa S.; Chang, Charles T.-C.; Duggan, Mark E.; Gould, Robert J.; Halczenko, Wasyl; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 16; (1994); p. 2537 - 2551 View in Reaxys With hydrogen, hydrogen cation, platinum(IV) oxide Asari, Tohru; Ishikawa, Shigetaka; Sasaki, Toshiki; Katada, Jun; Hayashi, Yoshio; et al.; Bioorganic & Medicinal Chemistry Letters; vol. 7; nb. 16; (1997); p. 2099 - 2104 View in Reaxys P.9.A : A. A. PIPERIDINE-4-ACETIC ACID STR47 4-Pyridylacetic acid (7 grams) (40.4 mmoles) was hydrogenated as described in Preparative Example 7 to give the product compound (Yield: 5.2 grams, 90percent, MH+ Patent; Schering Corporation; US5891872; (1999); (A1) English View in Reaxys 3 : 2-(4-N-t-Butyloxycarbonylpiperidine)ethanol (1-5) EXAMPLE 3 STR20 2-(4-N-t-Butyloxycarbonylpiperidine)ethanol (1-5) 4-pyridine acetic acid (50 g, 0.314 mole) was dissolved in H2 O (50 mL), and HOAc (100 mL), PtO2 (1 g) was added and the mixture was hydrogenated at 55 psi for 72 h. An additional 1 g of PtO2 was added after 48 h. The solution was filtered through celite, the cake was washed with H2 O and the filtrate was evaporated, using heptane to azeotrope off excess HOAc. The 4-piperidine acetic acid was obtained as a white solid. Rf (9:1 EtOH/H2 O) 0.11.1 H NMR (400 MHz, CD3 OD) 3.36 (bd, 2H), 330 (bt, 2H), 2.3 (d, J=7 Hz, 2H), 2.08 (m, 1H), 1.99 (bd, 2H), 1.47 (m, 2H). With acetic acid, PtO2 in n-heptane, water Patent; Merck and Co., Inc.; US5646000; (1997); (A1) English View in Reaxys P.5.A : A. A. PIPERIDINE-4-ACETIC ACID) STR57 4-Pyridylacetic acid (7 grams) (40.4 mmoles) was hydrogensted in water (100 ml) using 10percent Pd-C at 40 psi at 25 C. for 24 hours. The catalyst was filtered off and washed with water. The aqueous solution was shaken with BioRad AG1X8 resin (OH-form) (23 ml bed) and after 5 minutes the resin was filtered off and washed with water. The aqueous solution was evaporated to give the title compound (Yield: 5.2 grams, 90percent, MH+ 144). With Pd- C in water Patent; Schering Corporation; US5672611; (1997); (A1) English View in Reaxys P.17.A : A. A.
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Piperidine-4-Acetic Acid STR126 4-Pyridylacetic acid (7 grams) (40.4 mmoles) was hydrogenated as described in Preparative Example 15 to give the title compound (Yield: 5.2 grams, 90percent, MH+ 144). Patent; Schering Corporation; US5700806; (1997); (A1) English View in Reaxys P.17.A : A. A. PIPERIDINE-4-ACETIC ACID STR143 4-Pyridylacetic acid (7 grams) (40.4 mmoles) was hydrogenated as described in Preparative Example 15 to give the title compound (Yield: 5.2 grams, 90percent, MH+ 144). Patent; Schering Corporation; US5719148; (1998); (A1) English View in Reaxys
H N
Cl
Rx-ID: 5352044 View in Reaxys 18/224 Yield 95 % Conditions & References With hydrogen, acetic acid, platinum(IV) oxide in methanol, Time= 16h, T= 20 C , p= 750.06Torr , Catalytic hydrogenation Brundish, Derek; Bull, Alice; Donovan, Vera; Fullerton, Joseph D.; Garman, Sheila M.; Hayler, Judy F.; Janus, Diana; Kane, Peter D.; McDonnell, Mark; Smith, Garrick P.; Wakeford, Robert; Walker, Clive V.; Ambler, John; Butler, Keith; Talbot, Mark D.; Allen, Mark C.; Howarth, Graham; Hoyle, William; Kane, Peter D.; Journal of Medicinal Chemistry; vol. 42; nb. 22; (1999); p. 4584 - 4603 View in Reaxys
N
O S O N O O H Cl O HN
O NH O O N S O O
HN
Rx-ID: 24144746 View in Reaxys 19/224 Yield 88% Conditions & References P.C : Synthesis of N-(Toluene-4-sulfonyl)sarcosyl--(N-benzylpiperidin-4-yl)-D,L-alanine N-(Toluene-4-sulfonyl)sarcosyl-D,L--(4-pyridyl)alanine methyl ester (266 mg, 0.656 mmol) was dissolved in methanol (6 mL) and 12 N HCl (273 L) and PtO2 (25 mg) were added. The mixture was hydrogenated at 40 psi H2 for 4 hr. The mixture was filtered and the solvent was removed in vacuo to give N-(toluene-4-sulfonyl)sarcosyl-D,L--(4-piperidinyl)alanine methyl ester hydrochloride (260 mg, 88percent). With hydrogenchloride, H2, PtO2 in methanol Patent; Athena Neurosciences, Inc.; American Home Products Corp.; US6423688; (2002); (B1) English View in Reaxys
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Cl
N H
Rx-ID: 24439042 View in Reaxys 20/224 Yield 93% Conditions & References 118.C : 4-(2-Fluorobenzyl)1-(2-(4-fluorophenoxy)ethyl)piperidine hydrochloride STR154 C) 4-(2-Fluorobenzyl)piperidine hydrochloride. A mixture of 4-(2-fluorobenzyl)pyridine (5.83 g, 31.1 mmol) in a solution of MeOH (100 mL) and concd HCl (5.5 mL) with PtO2 (150 mg) was hydrogenated at 20 to 30 psi to yield the title compound as a colorless powder (6.66 g, 93percent): mp 187-188 C. 1 H NMR (D2 O) 1.34-1.54 (m, 2H), 1.78-1.98 (m, 3H), 2.63 (d, J=6.6 Hz, 2H), 2.89 (td, J=13 and 3.0 Hz, 2H), 3.32-3.43 (m, 2H), 3.78 (s, 3H), 7.06-7.17 (m, 2H), 7.23-7.31 (m, 2H). With concd HCl, PtO2 in methanol Patent; Warner-Lambert Company; Cocensys, Incorporated; US6124323; (2000); (A1) English View in Reaxys
H N
OH
NH
OH
NH
P O
O O
P O
Rx-ID: 5332013 View in Reaxys 21/224 Yield 100 % Conditions & References With hydrogen, palladium on activated charcoal in methanol, Time= 16h, T= 20 C , p= 750.06Torr , Catalytic hydrogenation Brundish, Derek; Bull, Alice; Donovan, Vera; Fullerton, Joseph D.; Garman, Sheila M.; Hayler, Judy F.; Janus, Diana; Kane, Peter D.; McDonnell, Mark; Smith, Garrick P.; Wakeford, Robert; Walker, Clive V.; Ambler, John; Butler, Keith; Talbot, Mark D.; Allen, Mark C.; Howarth, Graham; Hoyle, William; Kane, Peter D.; Journal of Medicinal Chemistry; vol. 42; nb. 22; (1999); p. 4584 - 4603 View in Reaxys
H N
Cl O OH
H O OH
Cl
Rx-ID: 2324668 View in Reaxys 22/224 Yield 100 % Conditions & References With hydrogen, palladium on activated charcoal in ethanol, Time= 24h Brodbeck, Robbin; He, Xiaoshu; Hodgetts, Kevin; Hutchison, Alan; Kieltyka, Andrzej; Kover, Renata X.; Peterson, John; Primus, Renee; Rachwal, Stanislaw; Thurkauf, Andrew; Wasley, Jan W.F.; Zhang, Xiaoyan; Zhao, He; Bioorganic and Medicinal Chemistry Letters; vol. 12; nb. 21; (2002); p. 3105 - 3109 View in Reaxys 100 % With platinum(IV) oxide, hydrogen in ethanol, water, T= 20 C , p= 2585.81Torr
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Pryde, David C.; Corless, Martin; Fenwick, David R.; Mason, Helen J.; Stammen, Blanda C.; Stephenson, Peter T.; Ellis, David; Bachelor, David; Gordon, David; Barber, Christopher G.; Wood, Anthony; Middleton, Donald S.; Blakemore, David C.; Parsons, Gemma C.; Eastwood, Rachel; Platts, Michelle Y.; Statham, Keith; Paradowski, Kerry A.; Burt, Catherine; Klute, Wolfgang; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 4; (2009); p. 1084 - 1088 View in Reaxys 58 % With hydrogen, rhodium on alumina in water, Time= 20h, p= 2250.2Torr Labouta, Ibrahim M.; Falch, Erik; Hjeds, Hans; Krogsgaard-Larsen, Povl; European Journal of Medicinal Chemistry; vol. 17; nb. 6; (1982); p. 531 - 535 View in Reaxys With hydrogen, acetic acid, platinum(IV) oxide, T= 40 - 45 C , p= 760Torr Ishihara, Yuji; Miyamoto, Masaomi; Nakayama, Takahiro; Goto, Giichi; Chemical & Pharmaceutical Bulletin; vol. 41; nb. 3; (1993); p. 529 - 538 View in Reaxys
NH F N
NH F NH
Rx-ID: 3455802 View in Reaxys 23/224 Yield 82 % Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, Time= 20h, p= 899.8Torr , Ambient temperature Malleron, Jean-Luc; Gueremy, Claude; Mignani, Serge; Peyronel, Jean-Francois; Truchon, Alain; et al.; Journal of Medicinal Chemistry; vol. 36; nb. 9; (1993); p. 1194 - 1202 View in Reaxys With hydrogen, acetic acid, Adam's catalyst Andree, Terrance H.; Meagher, Kristin L.; Mewshaw, Richard E.; Scerni, Rosemary; Schechter, Lee E.; Shi, Xiaojie; Smith, Deborah; Zhou, Dahui; Zhou, Ping; Bioorganic and Medicinal Chemistry Letters; vol. 12; nb. 3; (2002); p. 307 - 310 View in Reaxys 3 : Preparation of 5-Fluoro-3-(4-piperidinylmethyl)-1H-indole EXAMPLE 3 Preparation of 5-Fluoro-3-(4-piperidinylmethyl)-1H-indole A mixture of 5-fluoro-3-(4-pyridinylmethyl)-1H-indole (4.50 g, 20 mmol) and PtO2 (0.50 g, 2.2 mmol) in ethanol and acetic acid is hydrogenated under 45 psi at room temperature for 48 hr. After filtration of the catalyst and concentration of the filtrate, the residue is taken up with water, basified to pH 11 with 1N NaOH and extracted with CH2Cl2/iPrOH (3/1). The combined extracts are dried over Na2SO4 and concentrated in vacuo to give a pink solid. The solid is crystallized from EtOAc to afford the title compound as a white solid, 4.0 g (86percent) mp 155-157 C. (Lit. mp 163 C., Malleron et al, J. Med. Chem. 1193,36,1194). With acetic acid, PtO2 in ethanol Patent; American Home Products Corporation; US2002/128477; (2002); (A1) English View in Reaxys
F
Cl
N H
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Yield 91 %
Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, T= 60 C , p= 7500.75Torr Agai, Bela; Faigl, Ferenc; Proszenyak, Agnes; Vida, Laszlo; Tarkanyi, Gabor; European Journal of Organic Chemistry; nb. 17; (2004); p. 3623 - 3632 View in Reaxys
NH
Cl
F F F O
F
F O F
Rx-ID: 9690226 View in Reaxys 25/224 Yield 88 % Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, T= 65 C , p= 7500.75Torr Agai, Bela; Faigl, Ferenc; Proszenyak, Agnes; Vida, Laszlo; Tarkanyi, Gabor; European Journal of Organic Chemistry; nb. 17; (2004); p. 3623 - 3632 View in Reaxys
N HO
HO
NH
Cl
F F F O
F
F O F
F F F N F F F
F F F NH Cl F F F H
HN
F
F
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Yield 55 %
Conditions & References With hydrogenchloride, hydrogen, platinum on activated charcoal in acetic acid, Time= 16h, T= 60 C , p= 36200.4Torr Shanklin, James R.; Johnson, Christopher P.; Proakis, Anthony G.; Barrett, Richard J.; Journal of Medicinal Chemistry; vol. 34; nb. 10; (1991); p. 3011 - 3022 View in Reaxys
F N HO
HN HO
Rx-ID: 2776529 View in Reaxys 29/224 Yield 85 % Conditions & References With hydrogen, acetic acid, platinum on activated charcoal Walsh, David A.; Franzyshen, Stephen K.; Yanni, John M.; Journal of Medicinal Chemistry; vol. 32; nb. 1; (1989); p. 105 - 118 View in Reaxys 85% 42 : ,-Bis(4-fluorophenyl)-4-piperidineethanol PREPARATION 42 ,-Bis(4-fluorophenyl)-4-piperidineethanol A mixture of 12.25 g (0.0394 mole) of ,-bis(4-fluorophenyl)-4-pyridineethanol and 1.3 g of 5percent platinum on carbon catalyst in 250 ml of acetic acid was shaken under an atmosphere of hydrogen (53 psi) for 9 hr. The solution was filtered through Celite.(R)., and the solvent was removed in vacuo. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The solvent was removed in vacuo to give a solid. Recrystallization from acetonitrile gave 10.62 g (85percent yield) of title compound as a white, crystalline solid, mp 169-171 C. Analysis: Calculated for C19 H21 F2 NO: C, 71.90; H, 6.67; N, 4.41. Found: C, 71.98; H, 6.75; N, 4.54. With platinum in acetic acid Patent; A. H. Robins Company, Incorporated; US5070087; (1991); (A1) English View in Reaxys
N HO O O NH S O
NH HO O O NH S O
Rx-ID: 3463179 View in Reaxys 30/224 Yield 97 % Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, Time= 5.5h, T= 60 C , p= 2068.6Torr Chung, John Y. L.; Zhao, Dalian; Hughes, David L.; Grabowski, Edward J. J.; Tetrahedron; vol. 49; nb. 26; (1993); p. 5767 - 5776 View in Reaxys
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H N
Rx-ID: 9095838 View in Reaxys 31/224 Yield 100 % Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, Time= 7h, T= 80 C , p= 51714.8Torr Binet, Jean; Thomas, Didier; Benmbarek, Abdellah; Fornel, Daniel de; Renaut, Patrice; Chemical & Pharmaceutical Bulletin; vol. 50; nb. 3; (2002); p. 316 - 329 View in Reaxys 92% VIII : Preparation of N,N,,-tetramethyl-4-piperidineethanamine PREPARATION VIII Preparation of N,N,,-tetramethyl-4-piperidineethanamine A solution of 2 g (1.1*10-2 mole) of N,N,,-tetramethyl-4-pyridineethanamine in 400 ml of acetic acid was hydrogenated in a Parr's apparatus at 50 C. at a hydrogen pressure of 3.106 Pa in the presence of platinum dioxide. After eliminating the catalyst by filtering, the solvents were evaporated off under reduced pressure. The residue obtained was taken up in an aqueous 30percent sodium hydroxide solution and extracted with methylene chloride. The organic phase was washed, dried over magnesium sulphate and filtered and the solvents were evaporated off under reduced pressure. 1.9 g (yield: 92percent) of the desired compound was obtained as an oil. B Pt=60-64 C. under 0.02 mm Hg (i.e. about 2.66 Pa) With Adam's catalyst in hydrogen, acetic acid Patent; Fournier Industrie et Sante; US5614534; (1997); (A1) English View in Reaxys
Cl
N H
N
F HCl
HN
F F
Rx-ID: 29928859 View in Reaxys 33/224 Yield Conditions & References 6.2 :The mixture was dissolved in methanol (10 mL) and 1 M hydrochloric acid (10 mL) then catalytic platinum oxide was added and the resulting suspension was hydrogenated in a Parr apparatus at 40 psi for 3 d. Filtration through celite and concentration of the filtrate gave a complex mixture containing 20percent of the desired 4-(l,l-difluoroethyl)piperidine as the hydrochloride salt which was used without further purification. With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, water, Time= 72h, p= 2068.65Torr Patent; EXELIXIS, INC.; AAY, Naing; BLAZEY, Charles, M.; BOWLES, Owen, Joseph; BUSSENIUS, Joerg; CURTIS, Jeffry, Kimo; DEFINA, Steven, Charles; DUBENKO, Larisa; HARRIS, Jason, R.; JACKSON-UGUETO, Eileen,
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E.; KIM, Angie, Inyoung; MANALO, Jean-claire, Limun; PACK, Michael; PETO, Csaba, J.; RICE, Kenneth, D.; TSANG, Tsze, H.; WANG, Longcheng; WO2010/138490; (2010); (A1) English View in Reaxys 9.2 :The mixture was dissolved in methanol (10 mL) and 1 M hydrochloric acid (10 mL) then catalytic platinum oxide was added and the resulting suspension was hydrogenated in a Parr apparatus at 40 psi for 3 d. Filtration through celite and concentration of the filtrate gave a complex mixture containing 20percent of the desired 4-(l,l- difluoroethy piperidine as the hydrochloride salt which was used without further purification. With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 72h, p= 2068.65Torr Patent; EXELIXIS, INC.; RICE, Kenneth; WO2012/71509; (2012); (A2) English View in Reaxys
F
Cl
N H
H N
F OH
F OH
Cl
HN
HN
Cl
N N
HN
Rx-ID: 25123060 View in Reaxys 36/224 Yield 60% Conditions & References 27 : 4-[2-(4,5,6,7-Tetrahydro-1H-1,3-diazepin-2-yl)ethyl]piperidine EXAMPLE 27 4-[2-(4,5,6,7-Tetrahydro-1H-1,3-diazepin-2-yl)ethyl]piperidine The 4,5,6,7-tetrahydro-2[2-(4-pyridyl)ethyl]-1H-1,3-diazepine (1.9 g, 0.009 M) and PtO2 (0.25 g) in ethanol (20 ml) and 2 NHCl (15 ml) was reduced at 45 psig of hydrogen. After the hydrogenation, the solvent was removed and the residue was crystallized from ethanol-ether to give 1.5 g of 4-[2-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-yl)ethyl]piperidine (60percent yield) as dihydrochloride salt. With hydrogen, PtO2 in ethanol Patent; Hoffmann-La Roche Inc.; US4431653; (1984); (A1) English
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View in Reaxys
NH
Rx-ID: 25407506 View in Reaxys 37/224 Yield 75% Conditions & References 23 : 4-(1-Benzhydrylazetidin-3-yl)piperidine Preparation 23 4-(1-Benzhydrylazetidin-3-yl)piperidine Aqueous hydrochloric acid (1.0M, 200ml) was added to a solution of 4-(1-benzhydrylazetidin-3-yl)pyridine (Preparation 22) (29.7g, 99mmol) in methanol (300ml) and methanol (100ml) and water (100ml) then added. Platinum oxide (5.0g) was added and the reaction mixture was hydrogenated for 18 hours at 50C and a pressure of 414 kPa (60 p.s.i.). After this time, the reaction mixture was filtered through Arbocel (trade mark) filter aid and the solvent was removed under reduced pressure. A solution of sodium hydroxide (25g) in water (200ml) was added to the residue and the resultant mixture was extracted with diethyl ether (x3). The combined organic layers were dried over Na2SO4, filtered and solvent removed under reduced pressure to produce a solid. This solid was triturated with cold diisopropyl ether (50ml) to afford the title compound as a solid (22.7g, 75percent). 1H-NMR (CDCl ): = 7.10-7.40 (10H, m), 4.30 (1H, s), 3.20-3.40 (2H, m), 2.90-3.10 (2H, m), 2.60-2.80 (2H, m), 3 2.40-2.60 (2H, m), 2.10-2.30 (1H, m), 1.30-1.80 (4H, m), 0.80-1.00 (2H, m). With hydrogenchloride, sodium hydroxide in methanol, water Patent; PFIZER INC.; Pfizer Limited; EP992493; (2000); (A1) English View in Reaxys 1.c : 4-(3-Azetanyl)-1-(methylsulfonyl)piperidine1 c) 4-(1-Benzhydryl-3-azetanyl)piperidine To a solution of 4-(1-benzhydryl-3-azetanyl)pyridine (29.7g, 99mmol) in methanol (300ml) was added aqueous hydrochloric acid (1.0M, 200ml), a further portion of methanol (100ml), and water (100ml). To this mixture was added platinum (IV) oxide (5.0g) and the mixture was hydrogenated overnight at 50C and 414 kPa (60 p.s.i.). After this time the reaction was carefully filtered through Arbocel.(TM). (caution - fire hazard) and the filtrate retained. The solvent was evaporated under reduced pressure to remove most of the water. A solution of sodium hydroxide (25g) in water (200ml) was added and the resultant mixture was extracted three times with diethyl ether. The ethereal portion was dried over sodium sulphate, filtered and concentrated under reduced pressure to produce a solid which was triturated with cold diisopropyl ether (50 ml) to provide the title compound as a solid (22.7g). LRMS m/z = 307.2 (m+1)+ 1H-NMR (CDCl ): = 0.8-1 (m,2H), 1.3-1.8 (m,4H), 2.1-2.3 (m,1 H), 2.4-2.6 (m,2H), 2.6-2.8 (m,2H), 2.9-3.1 (m,2H), 3 3.2-3.4 (m,2H), 4.3 (s,1H), 7.1-7.4 (m,10H). With hydrogenchloride, sodium hydroxide in methanol, water Patent; Pfizer Limited; PFIZER INC.; EP962457; (1999); (A1) English View in Reaxys
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H N
NH
NH
Cl
Rx-ID: 5344276 View in Reaxys 38/224 Yield 100 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, Time= 16h, T= 20 C , Catalytic hydrogenation Brundish, Derek; Bull, Alice; Donovan, Vera; Fullerton, Joseph D.; Garman, Sheila M.; Hayler, Judy F.; Janus, Diana; Kane, Peter D.; McDonnell, Mark; Smith, Garrick P.; Wakeford, Robert; Walker, Clive V.; Ambler, John; Butler, Keith; Talbot, Mark D.; Allen, Mark C.; Howarth, Graham; Hoyle, William; Kane, Peter D.; Journal of Medicinal Chemistry; vol. 42; nb. 22; (1999); p. 4584 - 4603 View in Reaxys
F F
OH HCl
F F F
OH HCl
N H
Rx-ID: 8528697 View in Reaxys 39/224 Yield Conditions & References 1 :a) z-PrMgCl/THF/5C to RT b) H2/25 psi to 35 psi/MeOH c) K2C03/Cu20/145C to 170C/12-20 hours e) EDCYNaBH(O Ac)3/35C to 4O0C/ 3-20 hours f) EDC/35C to 5O0C/ 2-18 hours g) 80percentH2O2/MeOH/40C to 45C / 9-44 hours; In the first step as depicted in Example 1, an appropriately substituted aryl halide, for example, the known compound 4-bromo-l-(trifluoromethyl)benzene (A), and pyridine-4-carbaldehyde were reacted with a Grignard reagent to form the hydrogen chloride salt of 4-pyridyl[4-(trifluoromethyl)phenyl]methan-l-ol (B). Intermediate (B) was then hydrogenated under elevated pressure to afford the corresponding hydrogen chloride salt of 4-piperidyl[4- (trifluoromethyl)phenyl]methan-l-ol (C). Next, an appropriately substituted phenol, for example, the known compound 4-hydroxybenzaldehyde, was reacted with a halopyridine, for example 2-chloropyridine, in the presence of potassium carbonate and a catalytic amount of copper oxide at a temperature in the range of from 145 C to 170C to form 4-(2-pyridyloxy)benzaldehyde (D). Intermediate (C) was then reacted with Intermediate (D) in the presence of sodium triacetoxyborohydride at a temperature in the range of from 35 "C to 400C to form {l-[(4-(2- pyridyloxy)phenyl)methyl] (4-piperidyl)} [4-(trifluoromethyl)phenyl]methan- 1 -ol (F). Intermediate (F) was then condensed with an appropriately substituted aryl halide, for example the known compound 4-chlorobenxenisocyanate (G), at a temperature in the range of from 35C to 50C to form N-(4-chlorophenyl)({l-[(4- (2-pyridyloxy)phenyl)methyl](4-piperidyi)}[4- (trifluoromethyl)phenyl]methoxy)carboxamide (H). Intermediate (H) was then oxidized with hydrogen peroxide at a temperature in the range of from 40 C to 55C to forai N-(4-chlorophenyl)({l-oxo-l-[(4-(2-pyridyloxy)phenyl)methyl](4- piperidyl)} [4-(trifluoromethyl)phenyl]methoxy)carboxamide (Formula I) With hydrogen in methanol, T= 5 - 20 C , p= 1292.9 - 1810.07Torr Patent; FMC CORPORATION; WO2006/31764; (2006); (A2) English View in Reaxys
O H 2N
OH H
H 2N
OH O
NH
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Yield
Conditions & References a; 57.B :A solution of L-4-pyridylalanine 57-A (1.0 g), 10percent Pd/C (300 mg) in EtOH (40 mL) and 1 N HCl aqueous solution (20 mL) is shaken on Parr Shaker for 12 hours under a hydrogen atmosphere at 50 psi. The catalyst is filtered and the filtrate is concentrated to afford the piperidine 57-B. With hydrogenchloride, hydrogen, palladium 10 on activated carbon in ethanol, water, Time= 12h, p= 2585.81Torr Patent; IRM LLC; US2007/275906; (2007); (A1) English View in Reaxys
F F
F F F OH
OH HCl
N H
Rx-ID: 23423797 View in Reaxys 41/224 Yield Conditions & References 2.D :A solution of 6.4 grams (0.020 mole) of 4- (trifluoromethylphenyl)-4- pyridylmethanol in 80 mL of ethyl acetate was stirred, and dry hydrogen chloride gas was bubbled through the solution, thereby forming the hydrochloride salt of the pyridylmethanol intermediate. The salt was collected by filtration and washed with a small amount of ethyl acetate. The damp solid was then dissolved in 100 mL of methanol and placed in a Parr hydrogenation bottle, along with 0.5 gram (catalyst) of platinum oxide. The mixture was then hydrogenated at 45 pounds per square inch (psi) for about 75 minutes, using a Parr Hydrogenator. An NMR taken of the reaction mixture indicated that the reaction was about 90percent complete. An additional 0.25 gram of platinum oxide catalyst was added to the reaction mixture, and the hydrogenation at 45 psi was continued for an additional 60 minutes. After this time, the reaction mixture was filtered through diatomaceous earth. The filter cake was washed with methylene chloride and the combined wash and filtrate was concentrated under reduced pressure, yielding 5.2 grams of subject compound. The NMR spectrum was consistent with the proposed structure. The reaction was repeated. Stage 1: With hydrogenchloride in ethyl acetate Stage 2: With hydrogen, platinum(IV) oxide in methanol, Time= 2.25h, p= 2327.23Torr , Parr Hydrogenator Patent; FMC CORPORATION; WO2004/60371; (2004); (A1) English View in Reaxys
N
NH F
F F F
HCl
Rx-ID: 23770551 View in Reaxys 42/224 Yield Conditions & References 28 :Example 28 4-(trifluoromethyl)piperidine hydrochloride: Under atmosphere of argon, a solution of 4-(trifluoromethyl)pyridine (9.33g) in methanol (80mL) was added by concentrated hydrochloric acid (16mL) and platinum oxide (510mg) and stirred for three days at room temperature under hydrogen pressure. The reaction mixture was filtrated by celite (trade name) and the filtrate was concentrated. The residue was added by saturated sodium dicarbonate aqueous solution and extracted by ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and then filtrated. The filtrate was added by 4N hydrogen chloride/ethyl acetate solution (50mL) and then concentrated to give the title compound (13.0g) having the following physical data. TLC: Rf 0.13 (chloroform : methanol = 10 : 1); 1H NMR (CDCl3): 1.72 (dd, J= 13.0,4.0Hz, 1H), 1.81 (dd, J= 13.0, 4.0Hz, 1H), 2.05-2.20 (m, 2H), 2.41-2.80 (m, 1H), 3.06 (dt, J= 13.0, 3.0Hz, 2H), 3.40-3.60 (m, 2H). With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, water, Time= 72h, T= 20 C Patent; ONO PHARMACEUTICAL CO., LTD.; EP1666472; (2006); (A1) English View in Reaxys
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N
N
NH N
NH
NH
Rx-ID: 25136038 View in Reaxys 43/224 Yield 89% Conditions & References 18 : 4-[(4,5-Dihydro-1H-Imidazol-2-yl)methyl]piperidine EXAMPLE 18 4-[(4,5-Dihydro-1H-Imidazol-2-yl)methyl]piperidine 2-(4-pyridylmethyl)-imidazoline (3.0 g, 0.018 M) and platinum oxide (0.3 g) in ethanol (50 ml) and 2 N HCl (20 ml) was hydrogenated at 45 psig for 4 hrs. The catalyst was removed by filtration and the solvent was stripped. Crystallization from ethanol gave 4.05 g of 4-[(4,5-dihydro-1H-imidazol-2-yl)methyl]piperidine as dihydrochloride salt (89percent yield). With hydrogenchloride in ethanol Patent; Hoffmann-La Roche Inc.; US4431653; (1984); (A1) English View in Reaxys
O S N O
HN O S
O H Cl
Rx-ID: 28434299 View in Reaxys 44/224 Yield Conditions & References 72 :In a round bottom of flask was charged with 4-(3-methanesulfonyl-propyl)- pyridine (373 mg) and ethanol (5 ml_). Hydrochloric acid was added (1 ml_, 4N solution in dioxane) with stirring. The mixture was concentrated then the residue was taken in methanol and water. Platinum oxide (21 mg, 0.09 mmol, Aldrich) was added, and the mixture was hydrogenated at 60 psi overnight using a Parr apparatus. Upon completion, the mixture was filtered through Celite and washed thoroughly with methanol. The filtrate was concentrated to give 4-(3- methanesulfonyl-propyl)-pipehdine dihydrochloride as a white solid (480.7 mg, 85percent pure). Stage 1: With hydrogenchloride in 1,4-dioxane, ethanol Stage 2: With hydrogen, platinum(IV) oxide in methanol, water, p= 3102.97Torr Patent; F. HOFFMANN-LA ROCHE AG; WO2009/47161; (2009); (A1) English View in Reaxys
H N
OH Cl
OH Cl
Rx-ID: 9452229 View in Reaxys 45/224 Yield 76 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, Time= 0.5h, p= 2280Torr Ablordeppey; Altundas; Fan; Li; Lyles-Eggleston; Sikazwe; Xia; Yang; Zhang; Zhu; Borne; Schmidt; Shrihkande; Vanase-Frawley; Villalobos; Journal of Medicinal Chemistry; vol. 47; nb. 3; (2004); p. 497 - 508 View in Reaxys
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NH
Cl
F F F
F
O O N
O
NH
O N
N H
N
N H
Rx-ID: 10460957 View in Reaxys 47/224 Yield Conditions & References 86 %, 14 % With hydrogen, acetic acid, platinum (IV) oxide in ethanol, Time= 24h, T= 40 C , p= 45600Torr Spectr. Kurkin, A. V.; Sumtsova, E. A.; Yurovskaya, M. A.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 43; nb. 1; (2007); p. 34 - 40; Khimiya Geterotsiklicheskikh Soedinenii; nb. 1; (2007); p. 41 - 48 View in Reaxys
H N
Rx-ID: 26948 View in Reaxys 48/224 Yield 56 % Conditions & References With hydrogenchloride, samarium, Time= 0.166667h, Ambient temperature Kamochi, Yasuko; Kudo, Tadahiro; Chemical & Pharmaceutical Bulletin; vol. 43; nb. 8; (1995); p. 1422 - 1424 View in Reaxys With ethanol, sodium Ladenburg,A.; Justus Liebigs Annalen der Chemie; vol. 247; (1888); p. 70; Chemische Berichte; vol. 31; (1898); p. 290 View in Reaxys With nickel, T= 210 C , p= 110326 - 220652Torr , Hydrogenation Adams; Leonard; Journal of the American Chemical Society; vol. 66; (1944); p. 257,260 View in Reaxys 92 % Chro- With samarium diiodide in tetrahydrofuran, water, Time= 0.233333h, Ambient temperature mat. Kamochi, Yasuko; Kudo, Tadahiro; Heterocycles; vol. 36; nb. 10; (1993); p. 2383 - 2396 View in Reaxys With hydrogen, sodium, palladium on activated charcoal, 1.) ethanol, reflux, Multistep reaction Adomenas, P.; Sirutkaitis, R.; Molecular Crystals and Liquid Crystals (1969-1991); vol. 124; (1985); p. 269 - 276 View in Reaxys
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N
O OH
H N O OH
HO
HO
Rx-ID: 9448235 View in Reaxys 49/224 Yield 95 % Conditions & References With hydrogen, palladium on activated charcoal, Rh on carbon, Time= 2h, p= 76000Torr Bakker, Remko; De Esch, Iwan J. P.; Kitbunnadaj, Ruengwit; Leurs, Rob; Menge, Wiro M. P. B.; Timmerman, Henk; Vollinga, Roeland C.; Zuiderveld, Obbe P.; Kitbunnadaj, Ruengwit; Lutz, Martin; Spek, Anthony L.; Cavoy, Emile; Deltent, Marie-France; Journal of Medicinal Chemistry; vol. 46; nb. 25; (2003); p. 5445 - 5457 View in Reaxys 3-Piperidin-4-yl-propan-1-ol:; 4-Pyridinepropanol (10.0 g, 73 mmol) was dissolved in glacial acetic acid (50 mL). 10percent Palladium on carbon (1.1 g) was added and the mixture hydrogenated under 50 psi hydrogen gas for 6 days. The mixture was filtered through Celite and the solvent removed by rotary evaporation. The crude product 3-piperidin-4-ylpropan-l-ol (acetic acid salt) was used as obtained. 1H NMR (500 MHz, CDCl3) No. 6.3 (br), 3.65 (2H, t), 3.36 (2H, m), 2.79 (2H, dt), 2.01 (3H, s), 1.85 (2H, m), 1.7 - 1.3 (7H, m). With hydrogen, palladium 10 on activated carbon, Time= 144h, p= 2585.81Torr Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2005/103050; (2005); (A2) English View in Reaxys Preparation of 3-(3-(N-BOC-PIPERIDIN-4-YL)-PROPOXY)-PHENYLACETIC ACID 3-PIPERIDIN-4-YL-PROPAN-1-OL : 4-PYRIDINEPROPANOL (10.0 g, 73 mmol) was dissolved in glacial acetic acid (50 mL). 10percent Palladium on carbon (1.1 g) was added and the mixture hydrogenated under 50 psi hydrogen gas for 6 days. The mixture was filtered through Celite and the solvent removed by rotary evaporation. The crude product 3-piperidin-4-yl- PROPAN-1-OL (acetic acid salt) was used as OBTAINED.APOS;H NMR (500 MHz, CDCIA) 8 6.3 (br), 3.65 (2H, t), 3.36 (2H, m), 2.79 (2H, dt), 2.01 (3H, s), 1.85 (2H, m), 1.7-1. 3 (7H, m). With hydrogen, palladium 10 on activated carbon, Time= 144h, p= 2585.81Torr Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2004/41813; (2004); (A1) English View in Reaxys
O O N
O O N
N H
Rx-ID: 10460958 View in Reaxys 50/224 Yield 71 % Conditions & References With hydrogen, palladium on activated charcoal in ethyl acetate, Time= 10h, T= 80 C , p= 68400Torr Kurkin, A. V.; Sumtsova, E. A.; Yurovskaya, M. A.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 43; nb. 1; (2007); p. 34 - 40; Khimiya Geterotsiklicheskikh Soedinenii; nb. 1; (2007); p. 41 - 48 View in Reaxys
N N N
N N NH
Rx-ID: 25136044 View in Reaxys 51/224 Yield 70% Conditions & References 44 : 4-[2-(1-Ethyl-4,5-dihydro-imidazol-2-yl)ethyl]piperidine EXAMPLE 44
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4-[2-(1-Ethyl-4,5-dihydro-imidazol-2-yl)ethyl]piperidine The solution of 4-[2-(1-ethyl-4,5-dihydro-imidazol-2-yl)ethyl]-pyridine (1.1 g, 0.0054 M) in ethanol (15 ml) and water (15 ml) was added con.HCl (3 ml) and platinum oxide (0.2 g). The mixture was hydrogenated at 45 psig for 4 hrs. The catalyst was removed by filtration and the filtrate was stripped to dryness in vacuo. The residue was dissolved in methanol (25 ml) and sodium methoxide (0.011 M) was added and filtered. The filtrate was stripped to dryness and distilled at about 150 to about 175 C./0.2 mmHg to yield 4-[2-(1-ethyl-4,5dihydro-imidazol-2-yl)ethyl]piperidine as an oil (0.8 g, 70percent yield). With sodium methylate in methanol, ethanol, water Patent; Hoffmann-La Roche Inc.; US4431653; (1984); (A1) English View in Reaxys
H N
HO
HO
Rx-ID: 45121 View in Reaxys 52/224 Yield Conditions & References With sulfuric acid, water, platinum, T= 65 C , Hydrogenation Rabe; Journal fuer Praktische Chemie (Leipzig); vol. <2> 151; (1938); p. 65,79 View in Reaxys 45.A : Step A Step A Preparation of 4-piperidylmethanol 4-pyridylcarbinol (5.05 g, 45.8 mmol) dissolved in EtOH (75 ml) and concentrated HCl (3.81 ml, 45.8 mmol) was added. The starting material precipitated out and H2O was added until compound dissolved again (~10 ml), then PtO2 (1 g) was added. Stirred under H2 pressure (220 psi) overnight. The catalyst was filtered off and the solvent evaporated under reduced pressure to yield the slightly impure title compound (7.53 g, quantitative). This material was carried on directly to the next step without purification. With hydrogenchloride, PtO2 in ethanol, water Patent; Scarborough, Robert M.; Mehrotra, Mukund; Pandey, Anjali; Smyth, Mark; US2003/55244; (2003); (A1) English View in Reaxys
H N
Rx-ID: 1643511 View in Reaxys 53/224 Yield 86 % Conditions & References With hydrogen, Rh on carbon in ethanol, Time= 3h, p= 1500.1Torr Sucrow, Wolfgang; Schatull, Wolfgang; Zeitschrift fuer Naturforschung, Teil B: Anorganische Chemie, Organische Chemie; vol. 37; nb. 10; (1982); p. 1336 - 1338 View in Reaxys With hydrogen, sodium, palladium on activated charcoal, 1.) ethanol, reflux, Multistep reaction Adomenas, P.; Sirutkaitis, R.; Molecular Crystals and Liquid Crystals (1969-1991); vol. 124; (1985); p. 269 - 276 View in Reaxys
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H N
Rx-ID: 1750963 View in Reaxys 54/224 Yield 89 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol Cohen, Victor I.; Baumgold, Jesse; Jin, Biyun; Cruz, Rosanna De La; Rzeszotarski, Waclaw J.; Reba, Richard C.; Journal of Medicinal Chemistry; vol. 36; nb. 1; (1993); p. 162 - 165 View in Reaxys With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 24h, p= 2482.31Torr Bellucci, Cristina; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Martelli, Cecilia; Martini, Elisabetta; Scapecchi, Serena; Buccioni, Michela; Marucci, Gabriella; Matucci, Rosanna; Farmaco; vol. 59; nb. 12; (2004); p. 971 - 980 View in Reaxys
N HN O O
NH HN O O
Rx-ID: 11223648 View in Reaxys 55/224 Yield Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, p= 3102.97Torr Klimkowski, Valentine J.; Watson, Brian M.; Wiley, Michael R.; Liebeschuetz, John; Franciskovich, Jeffry B.; Marimuthu, Jothirajah; Bastian, Jolie A.; Sall, Daniel J.; Smallwood, Jeffrey K.; Chirgadze, Nikolay Y.; Smith, Gerald F.; et al.; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 21; (2007); p. 5801 - 5805 View in Reaxys 51 : Preparation 51; N-[L-PHENYL-4-(PIPERIDINE-4-YL) BUTYL] CARBAMIC acid tert- butyl ester. Agitating N- [L-PHENYL-4- (PYRIDIN-4-YL) butyl) carbamic acid tert-butyl ester (230 mg, 0.70 mmol) and a catalytic amount of platinum oxide in 25 mL of acetic acid under an atmosphere of hydrogen at 4.1 bar (60 psig) afforded, after filtration through diatomaceous earth and removal of solvent under reduced pressure, the title compound as a crude residue that was used without further purification. 1H NMR ES-MS m/e 333 (M+1) With hydrogen, acetic acid, platinum(IV) oxide, p= 3075.31Torr Patent; ELI LILLY AND COMPANY; WO2004/60872; (2004); (A1) English View in Reaxys
N H
Rx-ID: 24509551 View in Reaxys 56/224 Yield 88% Conditions & References 1.3 : Step 3 Step 3 A mixture of 4-(3-methoxybenzyl)pyridine (25 g, 126 mmol) and platinum oxide (2.4 g) in acetic acid (250 ml) was hydrogenated for 2 hr. The catalyst was removed and the solution concentrated in vacuo. The residue was dissolved in water and the solution basified with sodium hydroxide.
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The basic mixture was extracted with ether. The extracts were dried and concentrated in vacuo. The residue was vacuum distilled to give 4-(3-methoxy-benzyl)piperidine as an oil (22.6 g, 88percent). A sample of the hydrochloride was prepared in ether (mp: 146-147 C.). in water, acetic acid Patent; Bristol-Myers Squibb Co.; US5530012; (1996); (A1) English View in Reaxys 87.6% 11.3 : Step 3 Step 3 A mixture of 4-(3-methoxybenzyl)pyridine (25 g, 126 mmole) and platinum oxide (2.4 g) in acetic acid (250 ml) was hydrogenated for 2 hr. The catalyst was removed and the solution concentrated in vacuo. The residue was dissolved in water and the solution basified with sodium hydroxide. The basic mixture was extracted with ether. The extracts were dried and concentrated in vacuo. The residue was vacuum distilled to give 4-(3-methoxy-benzyl)piperidine as an oil (22.6 g, 87.6percent). A sample of the hydrochloride was prepared in ether (mp: 146-147 C.). Calc'd. for C13 H19 NO.HCl: C, 64.59percent; H, 8.34percent; N, 5.80percent. Found: C, 64.38percent; H, 8.34percent; N, 5.66percent. in water, acetic acid Patent; Briston-Myers Squibb; US5387593; (1995); (A1) English View in Reaxys
N H
Rx-ID: 80995 View in Reaxys 57/224 Yield Conditions & References With ethanol, sodium Tschitschibabin; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 34; (1902); p. 511; Chem. Zentralbl.; vol. 73; nb. II; (1902); p. 597 View in Reaxys With acetic acid, platinum, Hydrogenation Overhoff; Wibaut; Recueil des Travaux Chimiques des Pays-Bas; vol. 50; (1931); p. 957,976 View in Reaxys Veer; Goldschmidt; Recueil des Travaux Chimiques des Pays-Bas; vol. 65; (1946); p. 793 View in Reaxys Gray et al.; Journal of the American Chemical Society; vol. 79; (1957); p. 3805,3807 View in Reaxys With nickel, T= 100 C , p= 110326 - 220652Torr , Hydrogenation McElvain; Vozza; Journal of the American Chemical Society; vol. 71; (1949); p. 896,898 View in Reaxys
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H N
Cl
Rx-ID: 8851717 View in Reaxys 58/224 Yield 85 % Conditions & References With acetic acid, platinum(IV) oxide, Time= 24h, T= 20 C , p= 760Torr Colibretti, Maria Luisa; Imbimbo, Bruno P.; Lamperti, Giuseppina; Mandelli, Giacomina R.; Terni, Patrizia; Maiorana, Stefano; Chemical and Pharmaceutical Bulletin; vol. 48; nb. 11; (2000); p. 1611 - 1622 View in Reaxys
H N
O NH
O NH
Rx-ID: 9096561 View in Reaxys 59/224 Yield 93 % Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, Time= 7h, T= 80 C , p= 51714.8Torr Binet, Jean; Thomas, Didier; Benmbarek, Abdellah; Fornel, Daniel de; Renaut, Patrice; Chemical & Pharmaceutical Bulletin; vol. 50; nb. 3; (2002); p. 316 - 329 View in Reaxys
H N
Rx-ID: 9097420 View in Reaxys 60/224 Yield 100 % Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, Time= 7h, T= 80 C , p= 51714.8Torr Binet, Jean; Thomas, Didier; Benmbarek, Abdellah; Fornel, Daniel de; Renaut, Patrice; Chemical & Pharmaceutical Bulletin; vol. 50; nb. 3; (2002); p. 316 - 329 View in Reaxys
H N
2 HBr
NH N
NH N
Rx-ID: 9484452 View in Reaxys 61/224 Yield 52 % Conditions & References With hydrogen bromide, hydrogen, palladium on activated charcoal, Rh on carbon in ethanol, Time= 48h, p= 76000Torr
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Bakker, Remko; De Esch, Iwan J. P.; Kitbunnadaj, Ruengwit; Leurs, Rob; Menge, Wiro M. P. B.; Timmerman, Henk; Vollinga, Roeland C.; Zuiderveld, Obbe P.; Kitbunnadaj, Ruengwit; Lutz, Martin; Spek, Anthony L.; Cavoy, Emile; Deltent, Marie-France; Journal of Medicinal Chemistry; vol. 46; nb. 25; (2003); p. 5445 - 5457 View in Reaxys
N O
N H
Rx-ID: 24518244 View in Reaxys 62/224 Yield 76% Conditions & References 3.3 : Step 3 Step 3 A mixture of 4-(2-fluoro-5-methoxybenzyl)pyridine (7.7 g, 35.5 mmole) and platinum oxide (0.7 g) in acetic acid (75 ml) was hydrogenated for 3 hr. The catalyst was removed and the acetic acid removed in vacuo. The residue was dissolved in water and the solution basified with sodium hydroxide. The basic mixture was extracted with ether. The extracts were dried and concentrated in vacuo. The residue was vacuum distilled to give the product (6g, 76percent). in water, acetic acid Patent; Bristol-Myers Squibb Co.; US5530012; (1996); (A1) English View in Reaxys 75.9% 13.3 : Step 3 Step 3 A mixture of 4-(2-fluoro-5-methoxybenzyl)pyridine (7.7 g, 35.5 mmole) and platinum oxide (0.7 g) in acetic acid (75 ml) was hydrogenated for 3 hr. The catalyst was removed and the acetic acid removed in vacuo. The residue was dissolved in water and the solution basified with sodium hydroxide. The basic mixture was extracted with ether. The extracts were dried and concentrated in vacuo. The residue was vacuum distilled to give the product (6 g, 75.9percent). in water, acetic acid Patent; Briston-Myers Squibb; US5387593; (1995); (A1) English View in Reaxys
H N
Cl O
Cl O
Rx-ID: 920842 View in Reaxys 63/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, Time= 20h, T= 50 C , p= 3089.1Torr McCaustland,D.J. et al.; Journal of Medicinal Chemistry; vol. 17; nb. 9; (1974); p. 993 - 1000 View in Reaxys
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H N
Rx-ID: 1707063 View in Reaxys 64/224 Yield 91 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol Cohen, Victor I.; Baumgold, Jesse; Jin, Biyun; Cruz, Rosanna De La; Rzeszotarski, Waclaw J.; Reba, Richard C.; Journal of Medicinal Chemistry; vol. 36; nb. 1; (1993); p. 162 - 165 View in Reaxys
H N
H N
O N
Cl
O N
Cl
Rx-ID: 2325985 View in Reaxys 66/224 Yield 63.4 % Conditions & References With hydrogen, rhodium on alumina in water, Time= 20h, p= 2250.2Torr Labouta, Ibrahim M.; Falch, Erik; Hjeds, Hans; Krogsgaard-Larsen, Povl; European Journal of Medicinal Chemistry; vol. 17; nb. 6; (1982); p. 531 - 535 View in Reaxys
H N
O NH
O NH
Rx-ID: 2424346 View in Reaxys 67/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, T= 30 C , p= 2585.7Torr Alabaster, Valerie A.; Campbell, Simon F.; Danilewicz, John C.; Greengrass, Colin W.; Plews, Rhona M.; Journal of Medicinal Chemistry; vol. 30; nb. 6; (1987); p. 999 - 1003 View in Reaxys
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H N
H N
H N
Cl
Rx-ID: 2443339 View in Reaxys 70/224 Yield 81.5 % Conditions & References With hydrogen, platinum(IV) oxide in ethanol, Time= 24h, p= 2280Torr Goessinger,E.; Monatshefte fuer Chemie; vol. 113; (1982); p. 339 View in Reaxys
H N
F F
F F
Rx-ID: 2777266 View in Reaxys 71/224 Yield Conditions & References With hydrogen, platinum on activated charcoal in acetic acid, Time= 72h, T= 60 C , p= 2327.2Torr Shanklin, James R.; Johnson, Christopher P.; Proakis, Anthony G.; Barrett, Richard J.; Journal of Medicinal Chemistry; vol. 34; nb. 10; (1991); p. 3011 - 3022 View in Reaxys
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H N
F Cl H
Rx-ID: 2783068 View in Reaxys 72/224 Yield Conditions & References With hydrogen, platinum on activated charcoal in acetic acid, Time= 72h, T= 60 C , p= 2327.2Torr Shanklin, James R.; Johnson, Christopher P.; Proakis, Anthony G.; Barrett, Richard J.; Journal of Medicinal Chemistry; vol. 34; nb. 10; (1991); p. 3011 - 3022 View in Reaxys
N
HN
H N HN
H N HN
Rx-ID: 3472590 View in Reaxys 73/224 Yield 91 % Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, Time= 19h, p= 3040Torr , Ambient temperature Mokrosz, J. L.; Dukat, Malgorzata; Misztal, S.; Chojnacka-Wojcik, Ewa; Tatarczynska, Ewa; Pharmazie; vol. 45; nb. 10; (1990); p. 765 - 767 View in Reaxys
H N
OH
OH
Cl
Cl
Rx-ID: 9017646 View in Reaxys 74/224 Yield 100 % Conditions & References With hydrogen, platinum(IV) oxide, Time= 72h, T= 20 C , p= 3102.89Torr Jiang, Ji; Sane, David C.; Wang, Binghe; Wang, Wei; Bioorganic Chemistry; vol. 29; nb. 6; (2001); p. 357 - 379 View in Reaxys
Cl
Cl
O S N O NH O O
O S N O NH O O
N H
N H
NH
Rx-ID: 22983435 View in Reaxys 75/224 Yield Conditions & References B : GENERAL PROCEDURE B; General Procedure for the Preparation [OF CYCLOPROPYLPIPERIDINYLETHYL] acetamides [[00183]] 3- [3- (R, S)-2- (4-chloro-2, 5-dimethylbenzenesulfonyl)-4-oxo-2, 5-benzo- [DIAZEPIN-3-YL]-N- [2- (PYRID-4YL) ETH-1-YL] ACETAMIDE,] which can be prepared by amidation of the corresponding carboxylic acid with 2- (2aminoethyl) pyridine (TCI) in the manner described above is hydrogenated in the presence of platinum oxide [(PTO2)] in methanol to provide for 3- [3- (R, S)-2- (4-chloro-2, 5- dimethylbenzenesulfonyl)-4-oxo-2, 5- benzodiazepin-3-yl]-N[2- (piperidin-4- yl) eth-1-yl] acetamide. Sodium cyanoborohydride (1.5 mmol) is added to a stirred solution of 3- [3- (R,
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[S)-2- (4-CHLORO-2,] 5- dimethylbenzenesulfonyl)-4-oxo-2, [5-BENZODIAZEPIN-3-YL]-N-[2-(PIPERIDIN-4-YL) ETH-1-] yl] acetamide (1 mmol), with [1-ETHOXY-L-TRIMETHYLSILOXY] cyclopropane [(1] mmol) (Aldrich) and [ACOH] (1 mmol) in [MEOH] (20 mL) at rt. After being stirred at rt, the reaction mixture is refluxed for [18H.] The excess solvent is removed and washed with saturated [NAHC03] solution. The aqueous solution is extracted with [CH2C12] (2 x 100 mL). The combined organic layers are dried and concentrated. The resulting residue is then purified by silica gel column chromatography to afford the N-cyclopropylpiperidinylethyl acetamide derivative. With hydrogen, platinum(IV) oxide in methanol Patent; ELIAN PHARMACEUTICALS INC; WO2004/33436; (2004); (A1) English View in Reaxys
OH HO HCl
OH HO HCl
N H
Rx-ID: 23422030 View in Reaxys 76/224 Yield Conditions & References A.10.3 :OH OH HO t t-BuOH, 92percent The title compound was prepared as provided in Tetrahedron: Asymm. 1995,6, 505-518 (Reference for Sharpless asymmetric dihydroxylation); J. Org. Chem. 1965,30, 1331-1333; 1969 U. S. Patent No. 3,464, 997 (Reference for hydrogenation With hydrogenchloride, platinum(IV) oxide in methanol, water Patent; WARNER-LAMBERT COMPANY LLC; WO2005/26145; (2005); (A2) English View in Reaxys
H N O OH
HO
HO
Rx-ID: 23666935 View in Reaxys 77/224 Yield Conditions & References 17.A :Example 17; 3-(3-(N-Boc-piperidin-4-yl)-propoxy)-phenylacetic acid:; Step A: 4-Pyridinepropanol (10.0 g, 73 mmol) was dissolved in glacial acetic acid (50 mL). 10percent Palladium on carbon (1.1 g) was added and the mixture hydrogenated under 50 psi hydrogen gas for 6 days. The mixture was filtered through CeliteNo. and the solvent removed by rotary evaporation. The crude product 3-piperidin-4-ylpropan-1-ol (acetic acid salt) was used as obtained. 1H NMR (CDCl3) No. 6.3 (br), 3.65 (2H, t), 3.36 (2H, m), 2.79 (2H, dt), 2.01 (3H, s), 1.85 (2H, m), 1.7 - 1.3 (7H, m). With hydrogen, acetic acid, palladium 10 on activated carbon, Time= 144h, p= 2585.81Torr Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2005/105780; (2005); (A2) English View in Reaxys
Cl
Cl
S N
O
O H N O N
S N
H N O NH
N H
N H
Rx-ID: 23763574 View in Reaxys 78/224 Yield Conditions & References L.A :2- [2- (R, S)-1- (4-chloro-2, 5-dimethylbenzenesulfonyl)-3-oxo- 1,2, 3, 4-tetrahydroquinoxalin-2-yl]-N-[2-(pyrid-4yl) eth-1-yl] acetamide, prepared by amidation of the corresponding carboxylic acid with 2- (2-aminoethyl) pyridine (TCI) in the manner described above was hydrogenated in the presence of platinum oxide (PtO2) in methanol to provide for
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2- [2- (R, S)-1- (4-chloro-2, 5- dimethylbenzenesulfonyl)-3-oxo-1, 2,3, 4-tetra-hydroquinoxalin-2-yl]-N- [2- (piperidin-4yl) eth-1-yl] acetamide. With hydrogen, platinum(IV) oxide in methanol Patent; ELAN PHARMACEUTICALS, INC.; WO2003/93245; (2003); (A1) English View in Reaxys
HN HCl
Rx-ID: 24431476 View in Reaxys 79/224 Yield Conditions & References 141.A : 1-(2-(4-Hydroxyphenoxy)ethyl)-4-((2-naphthyl)methyl)piperidine hydrochloride STR177 A) 4-((2-Naphthyl)methyl)piperidine hydrochloride. A mixture of 4-((2-naphthyl) methyl)pyridine (750 mg, 3.42 mmol) and PtO2 (50 mg) in MeOH (25 mL) containing concd HCl (0.5 mL) was stirred under H2 at ambient pressure (balloon) for 19 h to yield the title compound as a pale yellow granular solid (324 mg): mp 215-217 C.; 1 H NMR (D2 O) 1.30-1.48 (m, 2H), 1.67-1.98 (m, 3H), 2.69 (d, J=6.9 Hz, 2H), 2.82 (td, J=13 and 3.0 Hz, 2H), 3.26-3.38 (m, 2H), 7.36 (d, J=8.4 Hz, 1H), 7.45-7.56 (m, 2H), 7.65 (s, 1H), 7.80-7.92 (m, 3H). With concd HCl, PtO2 in methanol Patent; Warner-Lambert Company; Cocensys, Incorporated; US6124323; (2000); (A1) English View in Reaxys
H N
F
F Cl H
Rx-ID: 24967300 View in Reaxys 80/224 Yield 1.06 g (95.2%) Conditions & References 17 : 4-[Bis(2,4-difluorophenyl)methyl]piperidine hydrochloride[1:1] PREPARATION 17 4-[Bis(2,4-difluorophenyl)methyl]piperidine hydrochloride[1:1] A mixture of 4-[bis(2,4-difluorophenyl)methyl]pyridine (23.84 g, 0.0752 mole) and 5percent platinum on carbon (2.0 g) was subjected to hydrogenation for three days at 60 C. in 400 ml of glacial acetic acid containing 3 mL of concentrated hydrochloric acid. This reaction was carried out at a pressure of 45 psi and 13.5 pounds of hydrogen gas was consumed. The reaction mixture was cooled to room temperature and filtered. Solvent was removed by rotary evaporator. The residue obtained was dissolved in chloroform and extracted with 5percent sodium hydroxide. The chloroform layer was dried over sodium sulfate and filtered. The chloroform was removed by rotary evaporator to give a dark residue (24.4 g, quantitative yield). A one-gram sample of this material was converted to the hydrochloride and the salt was recrystallized from methanoldiethyl ether. A white solid was obtained and dried in vacuo overnight at 80 C. This provided 1.06 g (95.2percent) of the title compound as a white, crystalline solid, mp 215-217 C. Analysis: Calculated for C18 H18 ClF4 N: C, 60.09; H, 5.04; N, 3.89. Found: C, 59.77; H, 5.02; N, 3.87. With hydrogenchloride, platinum in chloroform, acetic acid Patent; A. H. Robins Company, Incorporated; US5070087; (1991); (A1) English View in Reaxys
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OH HCl
OH
NH
Rx-ID: 25278177 View in Reaxys 81/224 Yield Conditions & References 5 : EXAMPLE 5 The mixture of 4.0 g of 4-(-hydroxy--methylphenethyl)-pyridine, 100 ml of glacial acetic acid, 20 ml of water and 2.0 g of 10percent palladium on charcoal is treated with hydrogen at 4.1 atm and room temperature. Following the theoretical uptake of hydrogen the reaction mixture is filtered to remove the catalyst. The filtrate is evaporated to dryness under reduced pressureand the residue treated with 50percent aqueous sodium hydroxide. The resulting mixture is extracted with methylene chloride; the extract is dried and evaporated under reduced pressure to give an oil which is converted into the hydrochloride with ethanolic hydrogen chloride to give 4-(-hydroxy--methylphenethyl)-piperidine hydrochloride of melting point 162-164. With sodium hydroxide, hydrogen, palladium on charcoal in water, acetic acid Patent; Ciba-Geigy Corporation; US3992546; (1976); (A1) English View in Reaxys
NH
NH
NH
Rx-ID: 3101023 View in Reaxys 82/224 Yield 75 % Conditions & References With hydrogen, Adam's catalyst in acetic acid, Ambient temperature Gueremy, Claude; Audiau, Francois; Champseix, Alain; Uzan, Andre; Fur, Gerard Le; Rataud, Jean; Journal of Medicinal Chemistry; vol. 23; nb. 12; (1980); p. 1306 - 1310 View in Reaxys
H N
Rx-ID: 3230590 View in Reaxys 83/224 Yield 96 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide, Time= 24h, p= 2280Torr Cohen, Victor I.; Jin, Biyun; Reba, Richard C.; Liebigs Annalen der Chemie; nb. 7; (1993); p. 809 - 810 View in Reaxys With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol Cohen, Victor I.; Baumgold, Jesse; Jin, Biyun; Cruz, Rosanna De La; Rzeszotarski, Waclaw J.; Reba, Richard C.; Journal of Medicinal Chemistry; vol. 36; nb. 1; (1993); p. 162 - 165 View in Reaxys With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 24h, p= 2482.31Torr
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Bellucci, Cristina; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Martelli, Cecilia; Martini, Elisabetta; Scapecchi, Serena; Buccioni, Michela; Marucci, Gabriella; Matucci, Rosanna; Farmaco; vol. 59; nb. 12; (2004); p. 971 - 980 View in Reaxys
NH
N
N
N H
N H
Rx-ID: 10531603 View in Reaxys 84/224 Yield Conditions & References 89 %, 11 % With platinum (IV) oxide in ethanol, trifluoroacetic acid, T= 60 C , p= 45600Torr Kurkin, A. V.; Sumtsova, E. A.; Yurovskaya, M. A.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 43; nb. 1; (2007); p. 34 - 40; Khimiya Geterotsiklicheskikh Soedinenii; nb. 1; (2007); p. 41 - 48 View in Reaxys
N O
NH O Cl H
O O
O O
Rx-ID: 23232925 View in Reaxys 85/224 Yield Conditions & References 2 : Example 2 The mixture of 5, 6-DIMETHOXY-2- (4-PYRIDYL) METHYL-1-INDANONE (45 gm), methanol (600 ML), concentrated hydrochloric acid (18 ml) and platinum oxide catalyst (2.5 gm) is taken into a hydrogenation flask and subjected to hydrogenation under a hydrogen gas pressure of 2 bars for 5 hours. The catalyst is filtered off and the solvents are evaporated completely under vacuum. Ethyl acetate (150 ML) is added to the residue and stirred for 15 minutes at 25C to 30C. Then the contents are cooled to 0C, stirred for 30 minutes and filtered to give 48 gm OF 4- [ (5, 6DIMETHOXY-1-INDANON)-2-YL] METHYLPIPERIDINE hydrochloride. With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, water, Time= 5h, p= 1500.15Torr Patent; HETERO DRUGS LIMITED; WO2005/3092; (2005); (A1) English View in Reaxys 2 :Example 2 PREPRATION of 2,3-dihydro-5, 6-dimethoxy-2- (4-piperidinyl) methyl-indan-1-one, hydrochloride A mixture OF 5, 6-DIMETHOXY-2- (4-PYRIDYL) METHYL-INDAN-1-ONE (25g from example 1), methanol (125ML), water (125ML), conc. hydrochloric acid (12. 5G) and platinum dioxide (2. 5G) was HYDROGENATED at 15 to 20 psi hydrogen pressure for about 6 hours. The reaction mixture was filtered, the filtrate was concentrated and the residue so obtained was crystallized from methanol to get the title compound (24G). HPLC Purity: 99.4percent. With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, water, Time= 6h, p= 775.743 - 1034.32Torr Patent; RANBAXY LABORATORIES LIMITED; WO2004/82685; (2004); (A1) English View in Reaxys 6 :4-[(5,6-Dimethoxy-l-indanon-2-yl)methyl]pyridine N-oxide (1Og) in methanol (100 ml) was hydrogenated in presence of cone, hydrochloric acid (l.lg) and palladium on activated carbon (Ig). The reaction mixture was filtered, filtrate was concentrated and residue so obtained was crystallized from acetone to get the title compound (9.5g). With hydrogenchloride, hydrogen, palladium on activated charcoal in methanol, Product distribution / selectivity Patent; JUBILANT ORGANOSYS LIMITED; WO2006/70396; (2006); (A1) English View in Reaxys
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OH
O OH
NH
OH
OH
Rx-ID: 23665379 View in Reaxys 86/224 Yield Conditions & References 8 :Shake a mixture of (S)-2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanol (21.1 g, 78 mmol), HOAc (400 mL) and Pt02 (370 mg) with H2 (50 psi) for 15 hr. Filter the mixture through celite and evaporate the solvent to give (S) - 2(2-isopropoxy-3- methylphenyl)-1-(4-piperidinyl)ethanol as the acetate salt; 1H-NMR (CDCl3) No. 7.1-6.9 (m, 2H), 4.2 (m, 1 H), 3.6 (m, 1 H), 3.4 (m, 2H), 2.9-2.7 (m, 4H), 2.3 (s, 3H), 2.0 (s, 3H), 2.1-1.5 (m, 5H), 1.3 (d, 6H). With hydrogen, platinum(IV) oxide, Time= 15h, p= 2585.81Torr Patent; AVENTIS PHARMACEUTICALS INC.; WO2005/111025; (2005); (A1) English View in Reaxys
H N
H N
O
O S
HO
HO
HO
Rx-ID: 24590767 View in Reaxys 87/224 Yield Conditions & References 84.b : 3-(Piperidin-4-yl)propan-1-ol p-toluenesulfonate: EXAMPLE 84b 3-(Piperidin-4-yl)propan-1-ol p-toluenesulfonate: To a solution of 3-(4-pyridyl)propan-1-ol (15.13 g, 0.1103 mol) in EtOH (100 mL) was added p-TsOH (20.98 g, 0.1103 mol) and PtO2 (1.5 g, 6.6 mmol). The resulting mixture was placed on a Parr apparatus and hydrogenated at 55 p.s.i. After 6 hr, the mixture was filtered (EtOH wash) and the filtrate concentrated in vacuo, giving 36.78 g (>100percent) of the desired piperidine; 1 H NMR (300 MHz, CDCl3) 7.7 (d, 2H), 7.2 (d, 2H), 3.55 (t, 2H), 3.3 (m, 4H), 2.95 (bt, 2H), 2.38 (s, 3H), 1.95 (bd, 2H), 1.58 (m, 2H), 1.3 (m, 3H). With p-TsOH, PtO2 in ethanol Patent; The Dupont Merck Pharmaceutical Company; US5563158; (1996); (A1) English View in Reaxys
Cl
NH N
NH
NH
Rx-ID: 25123061 View in Reaxys 88/224 Yield 87% Conditions & References 36 : 4-(1H-Imidazol-2-yl-methyl)-piperidine EXAMPLE 36 4-(1H-Imidazol-2-yl-methyl)-piperidine 2-(4-pyridylmethyl)imidazole (4 g, 0.025 M) and platinum oxide (0.4 g) in ethanol (40 ml) and 2 NHCl (50 ml) was hydrogenated at 45 psig for 4 hrs. The catalyst was removed by filtration and the filtrate was stripped to dryness. Crystallization from ethanol gave 4-(1H-imidazol-2-yl-methyl)piperidine as the dihydrochloride salt m.p. 251-252 C. (5.2 g, 87percent yield). in ethanol Patent; Hoffmann-La Roche Inc.; US4431653; (1984); (A1) English View in Reaxys
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NH
NH
NH
H N
Rx-ID: 1817809 View in Reaxys 90/224 Yield 90 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide, Time= 24h, p= 2280Torr Cohen, Victor I.; Jin, Biyun; Reba, Richard C.; Liebigs Annalen der Chemie; nb. 7; (1993); p. 809 - 810 View in Reaxys With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 24h, p= 2482.31Torr Bellucci, Cristina; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Martelli, Cecilia; Martini, Elisabetta; Scapecchi, Serena; Buccioni, Michela; Marucci, Gabriella; Matucci, Rosanna; Farmaco; vol. 59; nb. 12; (2004); p. 971 - 980 View in Reaxys
H N
Rx-ID: 2424016 View in Reaxys 91/224 Yield 95 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide, Time= 24h, p= 2280Torr Cohen, Victor I.; Jin, Biyun; Reba, Richard C.; Liebigs Annalen der Chemie; nb. 7; (1993); p. 809 - 810 View in Reaxys With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol Cohen, Victor I.; Baumgold, Jesse; Jin, Biyun; Cruz, Rosanna De La; Rzeszotarski, Waclaw J.; Reba, Richard C.; Journal of Medicinal Chemistry; vol. 36; nb. 1; (1993); p. 162 - 165 View in Reaxys
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NH
NH
Cl
Cl
NH
H N
Cl O OH
H
O OH
Rx-ID: 4348844 View in Reaxys 93/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, Yield given Chung, John Y. L.; Zhao, Dalian; Hughes, David L.; McNamara, James M.; Grabowski, Edward J. J.; Reider, Paul J.; Tetrahedron Letters; vol. 36; nb. 41; (1995); p. 7379 - 7382 View in Reaxys VI.a : a a Piperidin-4-ylacetic acid 75 g of 4-pyridylacetic acid hydrochloride are treated with 750 ml of glacial acetic acid (50percent strength), 6 g of platinum dioxide are added and the mixture is hydrogenated at 3 bar and room temperature in the course of 3 hours. The catalyst is filtered off with suction and the mother liquor is concentrated to dryness in vacuo. The residue is triturated with acetone and filtered off with suction. It is washed twice with acetone and once with ether. Yield: 71.7 g (92percent of theory) of white substance, Melting point: 150-153 C. With Adam's catalyst in acetic acid Patent; Karl Thomae; US5994356; (1999); (A1) English View in Reaxys
H N
O O
O O
Rx-ID: 4698895 View in Reaxys 94/224 Yield 98 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol Kassiou, Michael; Read, Roger W.; Shi, Xue-qin; Bioorganic & Medicinal Chemistry Letters; vol. 7; nb. 7; (1997); p. 799 - 804 View in Reaxys
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H N
Cl
OH
OH
Rx-ID: 5086355 View in Reaxys 95/224 Yield 100 % Conditions & References With hydrogenchloride, hydrogen, platinum on activated charcoal in water, Time= 264h, Ambient temperature Lygo; Wainwright; Crosby; Lowdon; Tetrahedron; vol. 55; nb. 9; (1999); p. 2795 - 2810 View in Reaxys
O HN
O HN
NH
Rx-ID: 5165864 View in Reaxys 96/224 Yield 100 % Conditions & References With hydrogenchloride, hydrogen, palladium on activated charcoal in ethanol Adang, Anton E. P.; De Zwart, Edwin; Gerritsma, Siene; Peters, Co A. M.; Veeneman, Gerrit; Bioorganic and Medicinal Chemistry Letters; vol. 9; nb. 9; (1999); p. 1227 - 1232 View in Reaxys
H N
NH O
NH O
Rx-ID: 5317806 View in Reaxys 97/224 Yield Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, Time= 16h, T= 20 C , Catalytic hydrogenation Brundish, Derek; Bull, Alice; Donovan, Vera; Fullerton, Joseph D.; Garman, Sheila M.; Hayler, Judy F.; Janus, Diana; Kane, Peter D.; McDonnell, Mark; Smith, Garrick P.; Wakeford, Robert; Walker, Clive V.; Ambler, John; Butler, Keith; Talbot, Mark D.; Allen, Mark C.; Howarth, Graham; Hoyle, William; Kane, Peter D.; Journal of Medicinal Chemistry; vol. 42; nb. 22; (1999); p. 4584 - 4603 View in Reaxys 1 : Preparation of 4-(2-Acetamidoethyl)piperidine STR20 PREPARATION 1 Preparation of 4-(2-Acetamidoethyl)piperidine STR20 4-(2-Acetamidoethyl)pyridine (33 g.) in ethanol (250 ml.) was acidified to pH 4 with hydrochloric acid and hydrogenated at 60 p.s.i./60 C. over a platinum oxide catalyst for 18 hours, after which time the uptake of hydrogen was complete. The catalyst was then removed by filtration and the filtrate was treated with a solution of potassium hydroxide flakes in methanol (1.1 molar equivalents) and refiltered. The solvents were distilled off in vacuo, leaving a clear oil, which on standing gave 4-(2-acetamidoethyl)piperidine (18 g.) as a white solid, m.p. 60 C. The oxalate salt was also prepared, m.p. 125-129 C. Analysis percent: Found: C, 50.9; H, 7.7; N, 10.4. Calculated for C9 H18 N2 O:C2 H2 O4: C, 50.8; H, 7.8; N, 10.8. With potassium hydroxide in methanol, ethanol Patent; Pfizer Inc.; US4370328; (1983); (A1) English View in Reaxys
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H N
O O
H N O O NH O O O
H N
NH O O
Rx-ID: 8591041 View in Reaxys 98/224 Yield 100 % Conditions & References With hydrogen, acetic acid, platinum(IV) oxide in ethanol, Hydrogenation Bergum, Peter W.; Brunck, Terence K.; Cohen, Cheryl R.; Goldman, Erick A.; Ho, Jonathan Z.; Levy, Odile E.; Nutt, Ruth F.; Reiner, John E.; Semple, J. Edward; Tamura, Susan Y.; Uong, Theresa H.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 8; (2000); p. 745 - 749 View in Reaxys
HO O H N O N O N N
HO O H N O N O N NH Cl H
Rx-ID: 8918319 View in Reaxys 99/224 Yield Conditions & References Stage 1: With hydrogen, palladium on activated charcoal in water, isopropyl alcohol, T= 75 C , p= 3102.89Torr Stage 2: With ethanol, C6H5N*HCl in dichloromethane, water, T= 40 C Andrews, Ian P; Atkins, Richard J; Badham, Neil F; Bellingham, Richard K; Breen, Gary F; Carey, John S; Etridge, Stephen K; Hayes, Jerome F; Hussain, Nigel; Morgan, David O; Share, Andrew C; Smith, Stephen A.C; Walsgrove, Timothy C; Wells, Andrew S; Tetrahedron Letters; vol. 42; nb. 29; (2001); p. 4915 - 4917 View in Reaxys
N HO
NH HO Cl H F F F F
NH
Cl
F F F
F
Rx-ID: 9689472 View in Reaxys 100/224 Yield Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, T= 70 C , p= 7500.75Torr Agai, Bela; Faigl, Ferenc; Proszenyak, Agnes; Vida, Laszlo; Tarkanyi, Gabor; European Journal of Organic Chemistry; nb. 17; (2004); p. 3623 - 3632 View in Reaxys
H N
Cl
Rx-ID: 24896346 View in Reaxys 101/224 Yield 59.13 g (80.3%) Conditions & References 23 : 4-(Diphenylmethyl)piperidine hydrochloride [1:1] PREPARATION 23
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4-(Diphenylmethyl)piperidine hydrochloride [1:1] A mixture of 62.69 g (0.256 mole) of diphenyl-4-pyridylmethane and 6.4 g of 10percent palladium on carbon (0.0060 mole) in 300 ml of glacial acetic acid and under an atmosphere of hydrogen (44 psi) was shaken on a Parr apparatus at 865 for 4 days. The reaction mixture was filtered, and the solvent was removed in vacuo from the filtrate. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over magnesium sulfate, and the solvent was removed in vacuo to give a solid. This was dissolved in a mixture of methanol-acetonitrile, and excess ethereal hydrogen chloride was added. A precipitate was collected to give 59.13 g (80.3percent) of slightly impure title compound as a white, crystalline solid, m.p. 273-274 C. Part of this was recrystallized from methanol-ether to give an analytically pure sample, m.p. 275.5-277 C. Analysis: Calculated for C18 H22 ClN: C, 75.11; H, 7.70; N, 4.87. Found: C, 75.03; H, 7.73; N, 4.93. With palladium in acetic acid, 3-hydroxy-propionitrile Patent; A. H. Robins Company, Incorporated; US4950674; (1990); (A1) English View in Reaxys 59.13 g (80.3%) 39 : 4-(Diphenylmethyl)piperidine hydrochloride [1:1] PREPARATION 39 4-(Diphenylmethyl)piperidine hydrochloride [1:1] A mixture of 62.69 g (0.256 mole) of 4-(diphenylmethyl)pyridine and 6.4 g of 10percent palladium on carbon (0.006 mole) in 300 ml of glacial acetic acid and under an atmosphere of hydrogen (44 psi) was shaken on a Parr apparatus at 85 for 4 days. The reaction mixture was filtered, and the solvent was removed in vacuo from the filtate. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over magnesium sulfate, and the solvent was removed in vacuo to give a solid. This was dissolved in a mixture of methanol-acetonitrile, and excess ethereal hydrogen chloride was added. A precipitate was collected to give 59.13 g (80.3percent) of slightly impure title compound as a white, crystalline solid, mp 273-274 C. Part of this was recrystallized from methanol-ether to give an analytically pure sample, mp 275.5-277 C. Analysis: Calculated for C18 H22 ClN: C, 75.11; H, 7.70; N, 4.87. Found: C, 75.03; H, 7.73; N, 4.93. With palladium in acetic acid, 3-hydroxy-propionitrile Patent; A. H. Robins Company, Incorporated; US5070087; (1991); (A1) English View in Reaxys
NH
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NH O
NH O
NH
H N
N O
N O
Rx-ID: 4841734 View in Reaxys 104/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, T= 60 C , p= 2280Torr Aubert, C.; Perrio-Huard, C.; Lasne, M. C.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 40; (1997); p. 752 - 754 View in Reaxys
H N
Cl O O
H O O
Cl
Rx-ID: 9075565 View in Reaxys 105/224 Yield 0.76 g Conditions & References With hydrogenchloride, hydrogen, platinum on activated charcoal in methanol, diethyl ether, Time= 15h, T= 20 C , p= 2068.59Torr Deutsch, Howard M.; Dunn, Travis; Ye, Xiaocong; Schweri, Margaret M.; Medicinal Chemistry Research; vol. 9; nb. 4; (1999); p. 213 - 222 View in Reaxys
O O
H N N
O O
H N NH
Rx-ID: 24070794 View in Reaxys 106/224 Yield Conditions & References ii : N-2-[1-(Methanesulfonyl)-4-piperidinyl]-1,1-dimethylethyll -N'-33-methoxy-4-(5-oxazolyl)phenyl]oxalamide ii) 2.1 g (8.4 mmol) of tert-butyl [1,1-dimethyl-2-(4-pyridyl)ethyl]carbamate, in 20 ml of methanol were hydrogenated with 400 mg of 10percent palladium on carbon catalyst at 70 C. and 7 Bar for 6 days. The resulting suspension was filtered, evaporated to dryness and the residue triturated with diethyl ether/petrol (1:9) to give 1.2 g of tert-butyl [1,1-dimethyl-2-(4-piperidinyl)ethyl]carbamate as a white solid. 1H NMR (400 MHz DMSO) :
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1.18 (6H,s), 1.28-1.41 (2H,m), 1.37 (9H,s), 1.52-1.69 (3H,m), 1.75-1.83 (2H,d), 2.74-2.84 (2H,t), 3.12-3.21 (2H,d), 6.40-6.48 (1H,br.s), 8.60-8.95 (1H,br.s). With palladium in methanol Patent; Broadhurst, Michael J.; Hill, Christopher H.; Hurst, David N.; Jones, Philip S.; Kay, Paul B.; Kilford, Ian R.; McKinnell, Robert M.; US2002/52513; (2002); (A1) English View in Reaxys ii : N-[2-[1-(Methanesulfonyl)-4-piperidinyl]-1,1-dimethylethyl]-N'-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamide ii) 2.1 g (8.4 mmol) of tert-butyl [1,1-dimethyl-2-(4-pyridyl)ethyl]carbamate, in 20 ml of methanol were hydrogenated with 400 mg of 10percent palladium on carbon catalyst at 70 C. and 7 Bar for 6 days. The resulting suspension was filtered, evaporated to dryness and the residue triturated with diethyl ether/petrol (1:9) to give 1.2 g of tert-butyl [1,1-dimethyl-2-(4-piperidinyl)ethyl]carbamate as a white solid. 1H NMR (400 MHz DMSO) : 1.18 (6H,s), 1.28-1.41 (2H,m), 1.37 (9H,s), 1.52-1.69 (3H,m), 1.75-1.83 (2H,d), 2.74-2.84 (2H,t), 3.12-3.21 (2H,d), 6.40-6.48 (1H,br.s), 8.60-8.95 (1H,br.s). With palladium in methanol Patent; Broadhurst, Michael J.; Hill, Christopher H.; Hurst, David N.; Jones, Philip S.; Kay, Paul B.; Kilford, Ian R.; McKinnell, Robert M.; US2002/52513; (2002); (A1) English View in Reaxys
NH
HO HCl F F F O O F F F F F F O
HO HCl O F F F
Rx-ID: 24588087 View in Reaxys 107/224 Yield Conditions & References 11.C : Synthesis of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine hydrochloride as an intermediate Step C Synthesis of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine hydrochloride as an intermediate A solution of 2.0 grams (0.004 mole) of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]pyridine hydrochloride and a catalytic amount of platinum oxide in 125 mL of methanol was hydrogenated at 50 psi of hydrogen in a Parr hydrogenator. The completion of hydrogenation required about two hours. After this time, the reaction mixture was filtered to remove the catalyst. The filtrate was concentrated to about 20 mL in volume, 80 mL of diethyl ether was added, and the solution was placed in a refrigerator. The resultant solid precipitate was collected by filtration, yielding about 0.4 gram of product. The filtrate was concentrated under reduced pressure, yielding an additional 1.9 grams of product. The two solid fractions were combined, yielding 2.3 grams of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine hydrochloride. The NMR spectrum was consistent with the proposed structure. With hydrogen in methanol, diethyl ether Patent; FMC Corporation; US5569664; (1996); (A1) English View in Reaxys Patent; FMC Corporation; US5639763; (1997); (A1) English View in Reaxys
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H N
O NH
HN O
N
Rx-ID: 35511061 View in Reaxys 108/224 Yield 50 % Conditions & References With platinum(IV) oxide, hydrogen in acetic acid, Time= 12h, T= 40 C , p= 2585.81Torr Blum, Charles A.; Dai, Han; Disch, Jeremy S.; Jin, Lei; Lavu, Siva; Perni, Robert B.; Schuman, Eli; Vlasuk, George P.; Belyanskaya, Svetlana L.; Chiu, Cynthia H.; Cuozzo, John W.; Evindar, Ghotas; Lind, Kenneth E.; Aquilani, Leah; Coppo, Frank; Deng, Jianghe; Graybill, Todd L.; Mao, Cheney; Journal of Medicinal Chemistry; vol. 56; nb. 9; (2013); p. 3666 - 3679 View in Reaxys
H N
Rx-ID: 1800140 View in Reaxys 109/224 Yield Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, Time= 16h, p= 2534.03Torr , Ambient temperature Shanklin, James R.; Johnson, Christopher P.; Proakis, Anthony G.; Barrett, Richard J.; Journal of Medicinal Chemistry; vol. 34; nb. 10; (1991); p. 3011 - 3022 View in Reaxys
H N
Cl 2 H
N
Rx-ID: 2742325 View in Reaxys 110/224 Yield Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in ethanol, isopropyl alcohol, p= 2068.6Torr Fabio, Paul F.; Lang, S. A.; Lin, Yang-i; Tomcufcik, Andrew S.; Journal of Medicinal Chemistry; vol. 23; nb. 2; (1980); p. 201 - 206 View in Reaxys
HN
Rx-ID: 2772956 View in Reaxys 111/224 Yield Conditions & References With hydrogen, palladium on activated charcoal in acetic acid, Time= 16h, p= 2534.03Torr , Ambient temperature
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Shanklin, James R.; Johnson, Christopher P.; Proakis, Anthony G.; Barrett, Richard J.; Journal of Medicinal Chemistry; vol. 34; nb. 10; (1991); p. 3011 - 3022 View in Reaxys
H N
N F
H N F
Cl
NH
NH
NH
Rx-ID: 3455784 View in Reaxys 114/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, Time= 20h, p= 899.8Torr , Ambient temperature, Yield given Malleron, Jean-Luc; Gueremy, Claude; Mignani, Serge; Peyronel, Jean-Francois; Truchon, Alain; et al.; Journal of Medicinal Chemistry; vol. 36; nb. 9; (1993); p. 1194 - 1202 View in Reaxys
NH
NH
NH
Rx-ID: 3455808 View in Reaxys 115/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, Time= 20h, p= 899.8Torr , Ambient temperature, Yield given Malleron, Jean-Luc; Gueremy, Claude; Mignani, Serge; Peyronel, Jean-Francois; Truchon, Alain; et al.; Journal of Medicinal Chemistry; vol. 36; nb. 9; (1993); p. 1194 - 1202 View in Reaxys
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NH
Rx-ID: 3628098 View in Reaxys 116/224 Yield Conditions & References With hydrogen, Rh/Al2O3 in ethanol, Time= 3h, p= 2585.7Torr , Ambient temperature Abou-Gharbia, Magid; Patel, Usha R.; Webb, Michael B.; Moyer, John A.; Andree, Terrance H.; Muth, Eric A.; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1382 - 1392 View in Reaxys
NH
NH
NH
H N
O OH
O OH
Rx-ID: 4944091 View in Reaxys 118/224 Yield Conditions & References With hydrogen, acetic acid, platinum(IV) oxide in methanol, Time= 16h, p= 2585.7Torr Klein, Scott I.; Molino, Bruce F.; Czekaj, Mark; Gardner, Charles J.; Chu, Valeria; et al.; Journal of Medicinal Chemistry; vol. 41; nb. 14; (1998); p. 2492 - 2502 View in Reaxys
H N
H N
N N
N NH
Rx-ID: 8385190 View in Reaxys 119/224 Yield Conditions & References 32 : EXAMPLE 32 EXAMPLE 32 A mixture of 1.5 g of 10-(4-pyridylmethyl)-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one, 100 ml of acetic acid, 5 ml of 1N hydrochloric acid and 0.19 g of platinum oxide is hydrogenated at a pressure of 56 bar for 18 hours at 50 C. After removal of the catalyst and the solvent a beige solid (1.5 g) is obtained, to which is added 100 ml of water; the suspension obtained is washed with 50 ml of dichloromethane, basified to pH 8 with saturated sodium hydrogen carbonate solution, washed again with twice 50 ml of dichloromethane and concentrated on a rotary evaporator. 250 ml of dimethylformamide, 20 ml of water and 3 g of silica are added to the residue obtained and the mixture is concentrated on a rotary evaporator.
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The evaporation residue is purified by chromatography on a column of silica (150 g partially deactivated with 3percent water), eluding with a mixture of chloroform, methanol and 28percent aqueous ammonia (24/6/1 by volume). 0.18 g of 10-(4-piperidylmethyl)-5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one is obtained, in the form of an orange solid N.M.R. spectrum: (300 MHz; (CD3)2 SO d6 with a few drops of CD3 COOD d4; in ppm): from 1.10 to 1.50 (mt, 5H: CH2 and CH of the piperidine); 2.05 to 2.35 (mt, 2H: CH2); 2.65 (mt, 2H: NCH2 of the piperidine axial H); 3.05 (broad d, J=12 Hz, 2H: NCH2 of the piperidine equatorial H); 4.30 (dd, J=9 and 3 Hz, 1H: H10); 7.30 and 7.40 (2t, J=8.5 Hz, 2H: H7 and H8); 7.62 and 7.88 (2d broad, J=8.5 Hz, 1H each: H6 and H9); 7.58 and 8.02 (2s broad, 1H each: --H of the[imidazole)]. With hydrogenchloride, ammonium hydroxide, acetic acid in N-methyl-acetamide, methanol, dichloromethane, water Patent; Rhone-Poulenc Rorer S.A.; US5753657; (1998); (A1) English View in Reaxys
H N
Rx-ID: 9824556 View in Reaxys 120/224 Yield 42 % Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 24h, p= 2482.31Torr Bellucci, Cristina; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Martelli, Cecilia; Martini, Elisabetta; Scapecchi, Serena; Buccioni, Michela; Marucci, Gabriella; Matucci, Rosanna; Farmaco; vol. 59; nb. 12; (2004); p. 971 - 980 View in Reaxys
H N
HN N
HN N
Rx-ID: 9902276 View in Reaxys 121/224 Yield Conditions & References With hydrogenchloride, hydrogen, palladium on activated charcoal in methanol, Time= 48h, p= 76000Torr Kitbunnadaj, Ruengwit; Hashimoto, Takeshi; Poli, Enzo; Zuiderveld, Obbe P.; Menozzi, Alessandro; Hidaka, Ryoko; Esch, Iwan J. P. de; Bakker, Remko A.; Menge, Wiro M. P. B.; Yamatodani, Atsushi; Coruzzi, Gabriella; et al.; Journal of Medicinal Chemistry; vol. 48; nb. 6; (2005); p. 2100 - 2107 View in Reaxys
O
N N N O
N N HN
Rx-ID: 23927452 View in Reaxys 122/224 Yield Conditions & References X : N,N-dimethyl-2-[methyl-(2-piperidin-4-yl-ethyl)-amino]-acetamide Of the crude N,N-dimethyl-2-[methyl-(2-pyridine-4-yl-ethyl)-amino]-acetamide, 44 g are dissolved in 500 ml of glacial acetic acid and hydrogenated with 4 g of PtO2 at ambient temperature under 3 bar H2. After the catalyst has been removed by suction filtering the filtrate is evaporated down. The residue is made alkaline with 50percent potassium hydroxide solution while cooling with ice and the product obtained is taken up in ether.
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The ether solution is dried over sodium sulphate, filtered and the solution is evaporated down. The product is left as a yellow oil. Yield: 42 g With potassium hydroxide in acetic acid Patent; Boehringer Ingelheim Pharma KG; US2003/171359; (2003); (A1) English View in Reaxys
N
N H NH
HN O
Rx-ID: 24068426 View in Reaxys 123/224 Yield Conditions & References 175.ii : (ii) (ii) N-(1-Piperidin-4-Yl-Ethyl)-Formamide N-(1-Pyridin-4-yl-ethyl)-formamide (1.86 g, 12.38 mmol) was dissolved in 50 ml of acetic acid. After addition of Rh (5percent on A1203, 307 mg) the mixture was hydrogenated with 10 bar hydrogen and 100 C. for 120 hours. The mixture was evaporated and lyophilised. The crude material was used without purification. With hydrogen in acetic acid Patent; Nazare, Marc; Will, David William; Peyman, Anuschirwan; Matter, Hans; Zoller, Gerhard; Gerlach, Uwe; US2002/198195; (2002); (A1) English View in Reaxys
HN
Rx-ID: 24215997 View in Reaxys 124/224 Yield Conditions & References 7 : EXAMPLE 7 This compound (12 g, 59 mmol) was subjected to hydrogenation reaction in acetic acid (200 ml) at a hydrogen pressure of 8 kg/cm2 in the presence of platinum oxide (300 ml) as a catalyst. The catalyst was filtered off, and the solvent was distilled off under reduced pressure. Then, a 10M sodium hydroxide aqueous solution (200 ml) was added thereto, and the solution was extracted with toluene (200 ml*2). The organic layer was dried on anhydrous sodium carbonate and then filtered, and the solvent was distilled off under reduced pressure to obtain 4-(4-propyl)cyclohexylpiperidine. With sodium hydroxide in acetic acid Patent; Chisso Corporation; US6576303; (2003); (B1) English View in Reaxys
O O HCl O O
O O HCl
HN
Rx-ID: 24293335 View in Reaxys 125/224 Yield Conditions & References XV.b : b b Diethyl 2-[2-(4-piperidinyl)-ethyl]malonate hydrochloride
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64.5 g (0.21 mol) of diethyl 2-[2-(4-pyridyl)-ethyl]malonate hydrochloride are hydrogenated exhaustively in 400 ml of absolute ethanol at room temperature under a hydrogen pressure of 50 psi over platinum dioxide as the catalyst. After the catalyst has been filtered off with suction, the solution which remains is concentrated to dryness in vacuo. The residue is brought to crystallization with acetone and is filtered off with suction. Yield: 62.8 g (95.5percent of theory) of highly hygroscopic crystals which deliquesce in air, Rf value: 0.22 (silica gel; methylene chloride/methanol=9:1) With Adam's catalyst in ethanol Patent; Dr. Karl Thomae GmbH; US5922717; (1999); (A1) English View in Reaxys
N N NH 2
HCl
HN N NH 2
Cl
Rx-ID: 24356323 View in Reaxys 126/224 Yield Conditions & References 48 : 1-Amino-3-(4-piperidyl)-3,4-dihydroisoquinoline hydrochloride EXAMPLE 48 1-Amino-3-(4-piperidyl)-3,4-dihydroisoquinoline hydrochloride A slurry of platinum oxide (8 mg, 10 moll) in methanol (1 ml) was added to a solution of 1-amino-3-(4-pyridyl)-3,4dihydroisoquinoline hydrochloride (Example 28) (150 mg, 0.578 mmol) in methanol and concentrated hydrochloric acid (0.4 ml), and stirred under 3 atmospheres of hydrogen for 16 h. The mixture was filtered through celite and evaporated. The residue was purified by RP-HPLC to yield a white hygroscope solid (126 mg). [M+H]+ 230; 360 MHz 1 H n.m.r (d6 -DMSO) 10.30 (1H, s), 9.43 (1H, s), 9.03 (1H, s), 8.80 (1H, br.s), 8.56 (1H, br.s), 8.05 (1H, d, J 7.8 Hz), 7.71 (1H, t, J 7.5 Hz), 7.54-7.50 (2H, m), 3.72-3.68 (1H, m), 3.27 (2H, d, J 13.2 Hz), 3.15 (1H, dd, J 17, 4 Hz), 2.99 (1H, dd, J 17.2, 6.9 Hz), 2.80-2.74 (2H, m), 1.95-1.63 (3H, m), 1.48-1.38 (2H, m). With hydrogenchloride in methanol Patent; Astra Pharmaceuticals, Ltd.; US6063789; (2000); (A1) English View in Reaxys
O O H N O N O N N
O O H N O N O N NH
Rx-ID: 24438782 View in Reaxys 127/224 Yield Conditions & References 2.c : c c methyl (R,S)-2,3,4,5-tetrahydro-4-isopentyl-3-oxo-8-[[[2-(4-piperidinyl)ethyl]methylamino]carbonyl]-1H-1,4-benzodiazepine-2-acetate A solution of the compound of Example 2(b) (0.2 mmol) and 0.6N hydrochloric acid (0.6 mL) in methanol (30 mL) was treated with platinum oxide (5 mg) and hydrogenated (45 psi) overnight. The mixture was filtered and concentrated to give the title compound. MS(ES) m/e 473 [M+H+. With hydrogenchloride in methanol Patent; SmithKline Beecham Corporation; US6117866; (2000); (A1) English View in Reaxys
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N
NH HCl HO
HO
Rx-ID: 24511334 View in Reaxys 128/224 Yield Conditions & References XX : 4-Hydroxymethyl-piperidine-hydrochloride EXAMPLE XX 4-Hydroxymethyl-piperidine-hydrochloride 25 g of 4-pyridylmethanol are hydrogenated in 300 ml of 50percent acetic acid in the presence of 2 g of platinum dioxide at ambient temperature and under a hydrogen pressure of 60 psi. After the uptake of hydrogen has ceased and the catalyst has been removed, the solvent is removed under reduced pressure. The solid residue is taken up in ether and then the hydrochloride is precipitated with ethereal hydrochloric acid. The precipitate is suction filtered and dried. Yield: 28.3 g (82percent of theory), Melting point: 120-125 C. With Adam's catalyst in acetic acid Patent; Dr. Karl Thomae GmbH; US5442064; (1995); (A1) English View in Reaxys
O O N HO O N
O O N HO O NH
Rx-ID: 24658457 View in Reaxys 129/224 Yield Conditions & References 19.e : e) e) Synthesis of [3-(piperidin-4-yl)-2,5-dioxopyrrolidin-1-yl]acetic acid 2.8 g of [3-(4-pyridyl)-2,5-dioxopyrrolidin-1-yl]acetic acid are suspended in 160 ml of acetic acid and hydrogenated in an autoclave at 100 C. and a hydrogen pressure of 150 bar for 24 h using 100 mg of 5percent rhodium on carbon as a catalyst. The catalyst is then filtered off and the filtrate is concentrated to dryness in vacuo. The product thus obtained is taken up in a little water and freeze-dried. Yield: 2.3 g MS(ES): 255 [M+H]+ With rhodium in hydrogen, acetic acid Patent; Hoechst Aktiengesellschaft; US5658935; (1997); (A1) English View in Reaxys
H N
Cl
Rx-ID: 24901951 View in Reaxys 130/224 Yield Conditions & References 34 : 4-[Bis(4-methylphenyl)methyl]piperidine hydrochloride [1:1] PREPARATION 34 4-[Bis(4-methylphenyl)methyl]piperidine hydrochloride [1:1] The free base of the title compound was prepared by hydrogenation of 4-[(bis-4-methylphenyl)methyl]pyridine in acetic acid using palladium on carbon as catalyst and converted to the hyrochloride salt in methanoldiethyl ether. The sale was recrystallized from methanol-ethyl ether and isopropanol-ethyl ether and dried overnight in vacuo at 80 C. White solid amounting to 46percent yield, m.p. 232 C. was obtained. With palladium in acetic acid
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Patent; A. H. Robins Company, Incorporated; US4950674; (1990); (A1) English View in Reaxys
N HN
N O
N NH O
NH
Rx-ID: 25036590 View in Reaxys 131/224 Yield Conditions & References 15 : Example 15 A mixture of 4.5 parts of N-(4-pyridinylmethyl)-2-benzoxazolamine and 120 parts of methanol was hydrogenated at normal pressure at about 50 C. with 2 parts of rhodium-on-charcoal catalyst 5percent. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated, yielding 4.6 parts of N-(4-piperidinylmethyl)-2-benzoxazolamine as an oily residue (intermediate 75). With rhodium-on-charcoal in methanol Patent; Janssen Pharmaceutica N.V.; US4689330; (1987); (A1) English View in Reaxys
N
HN
Rx-ID: 25131335 View in Reaxys 132/224 Yield Conditions & References 4.1 : (1) (1) Preparation of 2-[(4-piperidinyl)methyl]-2,3-dihydro-1-1H-indenone (or 2-[(4-piperidinyl)methyl]-1-indanone). 60 g of 2-[(4-pyridyl)methyl]-2,3-dihydro-1-1H-indenone in solution in 600 ml of acetic acid are hydrogenated at the ambient temperature, under a pressure of 1 bar of hydrogen, in the presence of 3 g of platinum oxide Adams. After 7 hours of hydrogenation, the catalyst is eliminated by filtration and the filtrate is evaporated. The residue is fixed on a column containing 1600 g of silica and eluted with a 90/10 chloroform-diethylamine mixture. 30.2 g of a purified product, in the form of the free base, are thus obtained. This product is converted into the hydrochloride. With hydrogen in acetic acid Patent; Pharmindustrie; US4357337; (1982); (A1) English View in Reaxys
H N
Rx-ID: 25134825 View in Reaxys 133/224 Yield Conditions & References 28 : Preparation of 4-(2-Methoxyethyl)piperidine Preparation 28 Preparation of 4-(2-Methoxyethyl)piperidine 4-(2-Methoxyethyl)pyridine (9.6 g), in a mixture of ethanol (100 ml) and 2 N hydrochloric acid (30 ml) was hydrogenated over platinum oxide at 50/50 p.s.i. until uptake of hydrogen ceased. The catalyst was removed by filtration and the solution evaporated in vacuo. The residue was then dissolved in water (50 ml), basified to pH 8 with dilute sodium hydroxide, and extracted with chloroform. The aqueous phase was evaporated in vacuo to give an oil which solidified on cooling. The solid was triturated with ether (60 ml), collected by filtration and dissolved in the minimum quantity of boiling ethyl acetate.
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The hot solution was filtered and on cooling deposited hygroscopic crystals of 4-(2-methoxyethyl)piperidine (9.9 g), m.p. 108-110. The structure was verified by i.r. and n.m.r. spectroscopy. With hydrogenchloride in ethanol, water, ethyl acetate Patent; Pfizer Inc.; US4289772; (1981); (A1) English View in Reaxys
O N
O NH
Rx-ID: 25193308 View in Reaxys 134/224 Yield Conditions & References R.4 : REFERENCE EXAMPLE 4 REFERENCE EXAMPLE 4 A solution of 4-(1,1-dimethyl-2-methoxyethyl)pyridine (10.0 g) in acetic acid (120 ml) was catalytically hydrogenated over platinum dioxide at 40 p.s.i. for 41 hours at from ambient temperature to 43 C. After 24 hours a further quantity of platinum dioxide was added, and a final addition was made after a further 8 hours. After a total of 41 hours the solution obtained after filtration of the catalyst was evaporated in vacuo and further evaporated after the addition of toluene to remove acetic acid. The resultant yellow oil was dissolved in dichloromethane and brought to pH12 with dilute aqueous sodium hydroxide solution. After saturation with sodium chloride, the organic phase was separated and the aqueous layer was re-extracted with five portions of dichloromethane. The combined organic solution was dried over anhydrous magnesium sulphate, and evaporated in vacuo to give 4(1,1-dimethyl-2-methoxyethyl)piperidine (9.7 g) as a straw-coloured oil. With Adam's catalyst in dichloromethane, acetic acid, toluene Patent; May and Baker Limited; US4871748; (1989); (A1) English View in Reaxys
O S N
O
O N
O S N NH Cl H
Rx-ID: 25207790 View in Reaxys 135/224 Yield Conditions & References 20 : PREPARATION 20 STR76 (This is slight alternative to the method of Preparation 10.) PREPARATION 20 STR76 (This is slight alternative to the method of Preparation 10.) A solution of 2-[2-(4-pyridyl)ethyl)]isothiazolidine-1,1-dioxide (186 g) in acetic acid (2.5 liters) was hydrogenated over platinum oxide catalyst (6.2 g) at 60 and 60 p.s.i. for 3 hours. The catalyst was filtered, the acetic acid solution was evaporated to small volume and the residue was dissolved in chloroform (1.5 liters). The chloroform solution was washed with aqueous sodium hydroxide solution (0.62 liters, 5N) and evaporated to dryness to give the crude product (167.3 g), as the free base. A sample of the free base (50 g) was dissolved in ethyl acetate (450 ml) and washed with aqueous sodium hydroxide solution (185 ml, 5N). The ethyl acetate solution was concentrated to low volume (150 ml) and a solution of HCl/isopropanol (42 ml, 5.71N) was added over 5 minutes. The resulting product, 2-[2-(4-piperidyl)ethyl]isothiazolidine-1,1-dioxide hydrochloride, was granulated at 0-5 for 2 hours, filtered and dried in vacuum at 40-50, yield 51.4 g, m.p. 191-193. Analysis percent: Found: C,44.4; H,7.9; N,10.5; Calculated for C10 H20 N2 SO2.HCl C,44.7; H,7.8; N,10.4. With hydrogenchloride in chloroform, acetic acid, ethyl acetate, isopropyl alcohol Patent; Pfizer Inc.; US4489075; (1984); (A1) English View in Reaxys
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O NH F N N N F F
O NH F N HN N F F
Rx-ID: 25411013 View in Reaxys 136/224 Yield Conditions & References 20 : 2,3,4,4a-Tetrahydro-3-[2-(4-Piperidinyl)Ethyl]-8-(Trifluoromethyl)-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One EXAMPLE 20 2,3,4,4a-Tetrahydro-3-[2-(4-Piperidinyl)Ethyl]-8-(Trifluoromethyl)-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One A mixture of 5 g. (0.014 mole) of 2,3,4,4a-tetrahydro-3-[2-(4-pyridinyl)ethyl]-8-trifluoromethyl-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one, 60 ml. of ethanol, 120 ml. of water, 12 ml. of concentrated hydrochloric acid and 1 g. of platinum oxide catalyst was hydrogenated in a Parr apparatus for 2 hours. The catalyst was filtered and the solvents removed. The residue was crystallized two times from methanol to yield 42 g. of the title compound as the dihydrochloride salt, m.p. 279-282 C. Analysis for: C19 H25 F3 N4 O.2HCl.CH3 OH. Calculated: C, 49.30; H, 6.41; N, 11.48; Cl, 14.54. Found: C, 49.77; H, 6.50; N, 11.65; Cl, 14.64. With hydrogenchloride in ethanol, water Patent; American Home Products Corporation; US4203987; (1980); (A1) English View in Reaxys
O NH N N N
O NH N HN N
Rx-ID: 25411014 View in Reaxys 137/224 Yield Conditions & References 15 : 2,3,4,4a-Tetrahydro-3-[2-(4-Piperidinyl)Ethyl]-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One EXAMPLE 15 2,3,4,4a-Tetrahydro-3-[2-(4-Piperidinyl)Ethyl]-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One A solution of 2,3,4,4a-tetrahydro-3-[2-(4-pyridinyl)ethyl]-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one in 120 ml. water and 60 ml. ethanol containing 13 ml. conc. hydrochloric acid was placed in a Parr hydrogenation apparatus, with 1.2 g. PtO2, under 45 psi. of hydrogen and shaken till pressure drop ceased. After filtering off catalyst the solvents were removed under vacuum and the residue crystallized from hot ethanol. Product filtered off, washed (ethanol), and dried. Dissolved in hot methanol which was displaced by ethanol by boiling off lower boiling solvent. Yield: 4.0 g. of the title compound as the dihydrochloride salt, m.p. 238-240 C. Analysis for: C18 H26 N4 O.2HCl.H2 O. Calculated: C, 53.33; H, 7.45; N, 13.82; Cl, 17.49. Found: C, 53.06; H, 7.12; N, 13.77; Cl, 17.43. With hydrogenchloride, hydrogen in methanol, ethanol, water Patent; American Home Products Corporation; US4203987; (1980); (A1) English View in Reaxys
N N O O
O O
N NH
Rx-ID: 25532514 View in Reaxys 138/224 Yield Conditions & References 24 : Ethyl (3-(2-(Piperidin-4-yl)ethyl)-3-azaspiro[5.5]undec-9-yl)acetate EXAMPLE 24 Ethyl (3-(2-(Piperidin-4-yl)ethyl)-3-azaspiro[5.5]undec-9-yl)acetate 0.17 g (0.5 mmol) of the compound from Example 22 were dissolved in 25 ml 90percent acetic acid followed by addition of 30 mg platinum(IV) oxide.
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The mixture was filled into an autoclave and hydrogenated for 4 h at room temperature and a pressure of 20 atm. The catalyst was removed by filtration and the solvent evaporated under reduced pressure. The residue was treated with water and neutralized with sodium carbonate followed by extraction with dichloromethane. The organic layer was dried over sodium sulfate and concentrated in vacuo to leave the pure title compound. yield: 0.04 g (23percent), brown resin With Adam's catalyst in water, acetic acid Patent; Eli Lilly and Company; COR Therapeutics Inc.; US6291469; (2001); (B1) English View in Reaxys
OH
OH
N H
Rx-ID: 9771094 View in Reaxys 139/224 Yield Conditions & References With sulfuric acid, hydrogen, platinum(IV) oxide in methanol, Time= 18h, T= 20 C Atkinson, Peter J.; Bromidge, Steven M.; Duxon, Mark S.; Gaster, Laramie M.; Hadley, Michael S.; Hammond, Beverley; Johnson, Christopher N.; Middlemiss, Derek N.; North, Stephanie E.; Price, Gary W.; Rami, Harshad K.; et al.; Bioorganic & Medicinal Chemistry Letters; vol. 15; nb. 3; (2005); p. 737 - 742 View in Reaxys With platinum(IV) oxide, sulfuric acid, hydrogen in methanol Armitage, Mark; Bret, Guillaume; Choudary, Bernie M.; Kingswood, Mike; Loft, Mike; Moore, Steve; Smith, Steve; Urquhart, Michael W. J.; Organic Process Research and Development; vol. 16; nb. 10; (2012); p. 1626 - 1634 View in Reaxys
HO
HN
HO
Rx-ID: 25053646 View in Reaxys 140/224 Yield Conditions & References 45 : Preparation of alpha,alpha-Bis(3-methoxyphenyl)-4-piperidineethanol EXAMPLE 45 Preparation of alpha,alpha-Bis(3-methoxyphenyl)-4-piperidineethanol A solution of alpha,alpha-bis(3-methoxyphenyl)-4-pyridine-ethanol (63 g) in acetic acid (400 ml) was hydrogenated over platinum oxide (2 g; 100 p.s.i.; 50). The reaction was stopped after the uptake of the theoretical amount of hydrogen (0.564 mol), then it was filtered to remove the catalyst and the solvent was evaporated under reduced pressure. After the residue was taken up in water (400 ml) and toluene (200 ml), the mixture was heated to reflux and then made basic with 10N sodium hydroxide. The mixture was cooled to 5, and the resulting solid was collected by filtration, then was washed in turn with water, toluene, toluene-hexane (1:1) and hexane to give, after drying, 62.5 g of alpha,alpha-bis(3-methoxyphenyl)-4-piperidineethanol, mp 111-113. With sodium hydroxide, hydrogen in hexane, water, acetic acid, toluene Patent; Hoffmann-La Roche Inc.; US4632925; (1986); (A1) English View in Reaxys
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H N
OH F F
OH F F
Rx-ID: 3582882 View in Reaxys 141/224 Yield 69 % Conditions & References With hydrogen, acetic acid, platinum on activated charcoal Walsh, David A.; Franzyshen, Stephen K.; Yanni, John M.; Journal of Medicinal Chemistry; vol. 32; nb. 1; (1989); p. 105 - 118 View in Reaxys
H N
OH F F F F F F
OH
F F
Rx-ID: 2778634 View in Reaxys 142/224 Yield 57 % Conditions & References With hydrogen, acetic acid, platinum on activated charcoal Walsh, David A.; Franzyshen, Stephen K.; Yanni, John M.; Journal of Medicinal Chemistry; vol. 32; nb. 1; (1989); p. 105 - 118 View in Reaxys
O NH
HN
O NH
Rx-ID: 9275179 View in Reaxys 143/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in methanol, p= 2068.59Torr Huang, Wenrong; Naughton, Mary Ann; Scarborough, Robert M.; Su, Ting; Yang, Hua; Zhu, Bing-Yan; Arfsten, Ann; Dam, Suiko; Edwards, Susan; Sinha, Uma; Wong, Paul W.; Hollenbach, Stanley; Bioorganic and Medicinal Chemistry Letters; vol. 13; nb. 4; (2003); p. 723 - 728 View in Reaxys
N
HN
Rx-ID: 919291 View in Reaxys 144/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, T= 50 C Marxer,A.; Helvetica Chimica Acta; vol. 52; nb. 25; (1969); p. 262 - 270 View in Reaxys
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H N
H N
Cl O
Cl O
H N
Cl
O Cl
H N
O O
O O
H N
N NH
N NH
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Yield
Conditions & References With hydrogen, Rh/Al2O3 in hydrogenchloride, Time= 48h, p= 2280Torr , Ambient temperature Nomoto, Yuji; Obase, Hiroyuki; Takai, Haruki; Hirata, Tadashi; Teranishi, Masayuki; et al.; Chemical & Pharmaceutical Bulletin; vol. 38; nb. 9; (1990); p. 2467 - 2471 View in Reaxys
H N
N HN O HN
N O
Rx-ID: 2481304 View in Reaxys 150/224 Yield Conditions & References With hydrogen, Rh/Al2O3 in hydrogenchloride, Time= 48h, p= 2280Torr , Ambient temperature Nomoto, Yuji; Obase, Hiroyuki; Takai, Haruki; Hirata, Tadashi; Teranishi, Masayuki; et al.; Chemical & Pharmaceutical Bulletin; vol. 38; nb. 9; (1990); p. 2467 - 2471 View in Reaxys
H N
Cl O OH
H O OH
Cl
Rx-ID: 3462423 View in Reaxys 151/224 Yield Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, T= 40 - 45 C , p= 760Torr Ishihara, Yuji; Miyamoto, Masaomi; Nakayama, Takahiro; Goto, Giichi; Chemical & Pharmaceutical Bulletin; vol. 41; nb. 3; (1993); p. 529 - 538 View in Reaxys
H N
HN O
HN O
Rx-ID: 4841282 View in Reaxys 152/224 Yield Conditions & References With hydrogen, platinum(IV) oxide in acetic acid, p= 2280Torr , Ambient temperature Aubert, C.; Perrio-Huard, C.; Lasne, M. C.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 40; (1997); p. 752 - 754 View in Reaxys
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N H
Rx-ID: 9903776 View in Reaxys 153/224 Yield Conditions & References With hydrogenchloride, hydrogen, palladium on activated charcoal in methanol, water, T= 60 - 65 C Proszenyak, Agnes; Agai, Bela; Tarkanyi, Gabor; Vida, Laszlo; Faigl, Ferenc; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 48; nb. 6; (2005); p. 421 - 428 View in Reaxys
H N
Cl 2 H N
N
Rx-ID: 539130 View in Reaxys 154/224 Yield Conditions & References With methanol, platinum, p= 2206.5 - 2942.03Torr , Hydrogenation Phillips; Journal of the American Chemical Society; vol. 79; (1957); p. 2836 View in Reaxys
N
2H
2H
2H
H
2H
Rx-ID: 1643512 View in Reaxys 155/224 Yield Conditions & References With diclazuril, deuterium, platinum(IV) oxide in water-d2, Time= 20h, p= 2068.6Torr , Ambient temperature Sheikh-Ali, Bashir M.; Khetrapal, C. L.; Weiss, Richard G.; Journal of Physical Chemistry; vol. 98; nb. 4; (1994); p. 1213 - 1216 View in Reaxys
NH
Rx-ID: 2175144 View in Reaxys 156/224 Yield Conditions & References With hydrogen, Adam's catalyst in acetic acid, Ambient temperature Gueremy, Claude; Audiau, Francois; Champseix, Alain; Uzan, Andre; Fur, Gerard Le; Rataud, Jean; Journal of Medicinal Chemistry; vol. 23; nb. 12; (1980); p. 1306 - 1310 View in Reaxys
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NH
Rx-ID: 3139805 View in Reaxys 157/224 Yield Conditions & References With hydrogen, Adam's catalyst in acetic acid, Ambient temperature Gueremy, Claude; Audiau, Francois; Champseix, Alain; Uzan, Andre; Fur, Gerard Le; Rataud, Jean; Journal of Medicinal Chemistry; vol. 23; nb. 12; (1980); p. 1306 - 1310 View in Reaxys
H N
O O
Cl
O O
Cl
Rx-ID: 4621870 View in Reaxys 158/224 Yield Conditions & References With hydrogen, palladium on activated charcoal in ethanol Dutta, Aloke K.; Coffey, Lori L.; Reith, Maarten E. A.; Journal of Medicinal Chemistry; vol. 40; nb. 1; (1997); p. 35 - 43 View in Reaxys
HN
N N
N N
Rx-ID: 9106822 View in Reaxys 159/224 Yield 0.180 g Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, Time= 7h, T= 20 C Kakefuda, Akio; Sakamoto, Shuichi; Suzuki, Takeshi; Tahara, Atsuo; Tobe, Takahiko; Tsukada, Junko; Tsukamoto, Shin-ichi; Tsukada, Junko; Journal of Medicinal Chemistry; vol. 45; nb. 12; (2002); p. 2589 - 2598 View in Reaxys
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H N
Rx-ID: 9826537 View in Reaxys 160/224 Yield Conditions & References With hydrogenchloride, hydrogen, platinum(IV) oxide in methanol, Time= 24h, p= 2482.31Torr Bellucci, Cristina; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Martelli, Cecilia; Martini, Elisabetta; Scapecchi, Serena; Buccioni, Michela; Marucci, Gabriella; Matucci, Rosanna; Farmaco; vol. 59; nb. 12; (2004); p. 971 - 980 View in Reaxys
H N
H N
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F
F
F
N F
N H
Rx-ID: 24518243 View in Reaxys 163/224 Yield Conditions & References 12.3 : Step 3 Step 3 A mixture of platinum oxide (0.5 g) and 4-(2,5-difluorobenzyl)pyridine from above in acetic acid (100 ml) was hydrogenated for 3 hr. The catalyst was removed and the solution concentrated in vacuo. The residue was dissolved in water and the solution basified with sodium hydroxide. The basic mixture was extracted with ether and the extracts concentrated in vacuo. The crude oil was vacuum distilled to give the product (5.1 g, 72.9percent, bp: 110 C.). A sample of the hydrochloride was prepared in ether (mp: 182-183 C.). Calc'd. for C12 H15 F2 N.HCl: C, 58.19percent; H, 6.52percent; N, 5.66percent. Found: C, 58.14percent; H, 6.56percent; N, 5.59percent. in water, acetic acid Patent; Briston-Myers Squibb; US5387593; (1995); (A1) English View in Reaxys
N HO
HN HO
Rx-ID: 25058921 View in Reaxys 164/224 Yield Conditions & References XXVII : 9-(4'-piperidinyl)-9-fluorenol EXAMPLE XXVII 9-(4'-piperidinyl)-9-fluorenol A solution of 13.0 g (0.05 mole) of 9-(4'-pyridyl)-9-fluorenol in 200 of glacial acetic acid was hydrogenated over 0.8 g of platinum oxide at 40 psi. The mixture was filtered, stripped, and the residue made basic affording 9-(4'-piperidinyl)-9-fluorenol. in acetic acid Patent; McNeilab, Inc.; US4251655; (1981); (A1) English View in Reaxys
OH N HO
HO OH NH
Rx-ID: 25208997 View in Reaxys 165/224 Yield Conditions & References 5 : Preparation 5 STR66 A solution of 2-(4-pyridyl)propane-1,2-diol (2.0 g) in acetic acid (30 cm3) was hydrogenated over platinum oxide (0.10 g) at 60 and 60 p.s.i. pressure for 16 hours. The catalyst was removed by filtration through "Avicel" and volatile material was removed in vacuo to afford 2-(4piperidyl)propan-1,2-diol (2.1 g). (Crude acetate salt, oil). Also prepared by a similar method from the appropriate pyridine starting materials were: in acetic acid Patent; Pfizer Inc.; US4542132; (1985); (A1) English
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View in Reaxys
F F F N
HN
F F F
Rx-ID: 25343117 View in Reaxys 166/224 Yield Conditions & References 10.B : EXAMPLE 10 A solution of 15.7 parts of 4-[-(p-trifluoromethylphenyl)benzyl]pyridine in 250 parts of acetic acid is heated, with agitation, at 47 C. under approximately 4 atmospheres of hydrogen and in the presence of 2 parts of platinum oxide catalyst for 2 hours. The resultant mixture is filtered, and the filtrate is stripped of solvent by vacuum distillation. The residue is poured into 3 volumes of ice water, and the mixture thus obtained is made alkaline with sodium hydroxide. This mixture is then extracted with ether. The ether extract is dried over anhydrous potassium carbonate, filtered, and the ether removed to provide 4-[(4-trifluoromethylphenyl)phenylmethyl]piperidine as an oil. in (2S)-N-methyl-1-phenylpropan-2-amine hydrate, acetic acid Patent; G. D. Searle and Co.; US4105849; (1978); (A1) English View in Reaxys
H N
O S O
NH
O S O
NH
Rx-ID: 25349705 View in Reaxys 167/224 Yield Conditions & References 1.B : (B) (B) Preparation of 4-(2-methanesulphonamidoethyl)piperidine STR13 4-(2-Methanesulphonamidoethyl)pyridine (8.4 g.) in ethanol (85 ml.) was acidified to pH 2 with 2 N HCl and hydrogenated at room temperature and a pressure of 50 p.s.i. over a platinum oxide catalyst until hydrogen uptake ceased. The catalyst was then removed by filtration and the filtrate was taken to dryness in vacuo to give a white solid which was dissolved in the minimum volume of hot ethanol, filtered quickly, and left at room temperature overnight. The resultant white crystals were collected by filtration and dried to yield 4-(2-methanesulphonamidoethyl)piperidine:hydrochloride (8.3 g.), m.p. 165-167 C. Analysis percent: Found: C, 39.6; H, 7.8; N, 11.7: Calculated for C8 H18 N2 O2 S:HCl: C, 39.6; H, 7.9; N, 11.5. in ethanol Patent; Pfizer Inc.; US4188391; (1980); (A1) English View in Reaxys
H N
Rx-ID: 320074 View in Reaxys 168/224 Yield Conditions & References With nickel, T= 180 C , p= 147102Torr , Hydrogenation Profft; Solf; ; vol. 2; (1959); p. 273,275
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View in Reaxys With sodium, butan-1-ol, Hydrieren des Reaktionsprodukts an Palladium/Kohle in Essigsaeure Wawzonek et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2894 View in Reaxys With hydrogen, sodium, 1.) ethanol, reflux, Multistep reaction Adomenas, P.; Sirutkaitis, R.; Molecular Crystals and Liquid Crystals (1969-1991); vol. 124; (1985); p. 269 - 276 View in Reaxys
N
O OH
H N O OH
Rx-ID: 1537033 View in Reaxys 169/224 Yield Conditions & References With hydrogen, palladium on activated charcoal, T= 100 C Bellamy, Francois D.; Chazan, Jean B.; Dodey, Pierre; Dutartre, Patrick; Ou, Khan; et al.; Journal of Medicinal Chemistry; vol. 34; nb. 5; (1991); p. 1545 - 1552 View in Reaxys
N
O OH
H N O OH
Rx-ID: 1557526 View in Reaxys 170/224 Yield Conditions & References With hydrogen, palladium on activated charcoal, T= 100 C Bellamy, Francois D.; Chazan, Jean B.; Dodey, Pierre; Dutartre, Patrick; Ou, Khan; et al.; Journal of Medicinal Chemistry; vol. 34; nb. 5; (1991); p. 1545 - 1552 View in Reaxys
H N
HO
HO
Rx-ID: 25048892 View in Reaxys 171/224 Yield Conditions & References 1.i : (b) (i) The N-benzoyl-4-phenoxymethylpiperidine used as starting material is obtained as follows: 4-Hydroxymethylpyridine is hydrogenated in methanol at 140 C. under 200 atmospheres of hydrogen pressure in the presence of ruthenium oxide, producing 4-hydroxymethylpiperidine, b.p. 126-130 C./14 mm Hg; m.p. 55-56 C. in methanol Patent; Boehringer Mannheim GmbH; US4243807; (1981); (A1) English View in Reaxys
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N
OH O OH E O HN
H N
Rx-ID: 25058922 View in Reaxys 172/224 Yield Conditions & References XXX : 9-(4'-Piperidyl)fluorene fumarate EXAMPLE XXX 9-(4'-Piperidyl)fluorene fumarate A solution of 54.75 g (0.225 mole) of 9-(4'-pyridyl)fluorene in 600 ml of acetic acid was hydrogenated over 5.0 g of platinum oxide at 40 psi and 25 C. The mixture was filtered, stripped and made basic, affording 9-(4'-piperidyl)fluorene, which was crystallized as the fumarate salt, m.p. 228-230 C. (dec). in acetic acid Patent; McNeilab, Inc.; US4251655; (1981); (A1) English View in Reaxys
H N
OH
OH
Rx-ID: 72352 View in Reaxys 173/224 Yield Conditions & References With sodium, butan-1-ol, und Hydrieren des vermutlich als 2-<1,2,3,6-Tetrahydro-<4>pyridyl>-aethanol C7H13NO zu formulierenden Reaktionsprodukts in Essigsaeure an Palladium Wawzonek et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2894 View in Reaxys Lukes et al.; Collection of Czechoslovak Chemical Communications; vol. 22; (1957); p. 1173,1177 View in Reaxys With acetic acid, platinum, Hydrogenation Burtner; Brown; Journal of the American Chemical Society; vol. 69; (1947); p. 630,631 View in Reaxys
H N
Rx-ID: 51509 View in Reaxys 174/224 Yield Conditions & References With sodium, butan-1-ol, Hydrieren des Reaktionsprodukts an Palladium/Kohle in Essigsaeure Wawzonek et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2894 View in Reaxys With hydrogen, sodium, palladium on activated charcoal, 1.) ethanol, reflux, Multistep reaction Adomenas, P.; Sirutkaitis, R.; Molecular Crystals and Liquid Crystals (1969-1991); vol. 124; (1985); p. 269 - 276 View in Reaxys
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H N
O O
Cl
O O
Rx-ID: 539277 View in Reaxys 175/224 Yield Conditions & References With ethanol, platinum, Hydrogenation Jachontow; Rubzow; Zhurnal Obshchei Khimii; vol. 27; (1957); p. 72,75; engl. Ausg. S. 83, 85 View in Reaxys With acetic acid, platinum, Hydrogenation Leonard et al.; Journal of the American Chemical Society; vol. 75; (1953); p. 6249,6251 View in Reaxys
H N
OH
OH
Rx-ID: 26053285 View in Reaxys 176/224 Yield Conditions & References With hydrogen, acetic acid, platinum(IV) oxide, Time= 96h, p= 3102.97Torr Desaubry, Laurent; Riche, Stephanie; Laeuffer, Patricia; Cazenave, Jean-Pierre; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 6; (2008); p. 2028 - 2031 View in Reaxys
H N
2H
F
N
2H
Rx-ID: 13152116 View in Reaxys 177/224 Yield Conditions & References Reaction Steps: 2 1: hydrogen; hydrochloric acid / Pd/C / methanol; H2O / 60 - 65 C 2: [2H4]-methanol; deuterium chloride / Pd/C / D2O / 6 h / 60 C / 2250.18 Torr With hydrogenchloride, methanol-d4, hydrogen, DCl, palladium on activated charcoal in methanol, water, water-d2 Proszenyak, Agnes; Agai, Bela; Tarkanyi, Gabor; Vida, Laszlo; Faigl, Ferenc; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 48; nb. 6; (2005); p. 421 - 428 View in Reaxys
H N
Cl O
Cl O (+)-enantiomer
Rx-ID: 22768908 View in Reaxys 178/224 Yield Conditions & References Reaction Steps: 2
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1: H2 / PtO2 / acetic acid / 50 C 2: Dg-tartaric acid / ethanol With (2S,3S)-2,3-dihydroxybutanedioic acid, hydrogen, platinum(IV) oxide in ethanol, acetic acid Marxer,A.; Helvetica Chimica Acta; vol. 52; nb. 25; (1969); p. 262 - 270 View in Reaxys
H N
Cl O
Cl O (-)-enantiomer
Rx-ID: 22768909 View in Reaxys 179/224 Yield Conditions & References Reaction Steps: 2 1: H2 / PtO2 / acetic acid / 50 C 2: Dg-tartaric acid / ethanol With (2S,3S)-2,3-dihydroxybutanedioic acid, hydrogen, platinum(IV) oxide in ethanol, acetic acid Marxer,A.; Helvetica Chimica Acta; vol. 52; nb. 25; (1969); p. 262 - 270 View in Reaxys
H N
H N
Rx-ID: 34992 View in Reaxys 180/224 Yield Conditions & References With sodium, butan-1-ol Wawzonek et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2894 View in Reaxys Lukes; Ferles; Collection of Czechoslovak Chemical Communications; vol. 20; (1955); p. 1227,1232 View in Reaxys
H N
Rx-ID: 43538 View in Reaxys 181/224 Yield Conditions & References With nickel, Hydrogenation McElvain; Carney; Journal of the American Chemical Society; vol. 68; (1946); p. 2592,2599 View in Reaxys
H N
Rx-ID: 83569 View in Reaxys 182/224 Yield Conditions & References With acetic acid, platinum, Hydrogenation
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Norton et al.; Journal of the American Chemical Society; vol. 68; (1946); p. 1572,1575 View in Reaxys
H N
Rx-ID: 142909 View in Reaxys 183/224 Yield Conditions & References With hydrogenchloride, ethanol, platinum, Hydrogenation Harris et al.; Journal of the American Chemical Society; vol. 73; (1951); p. 3959,3960, 3962 View in Reaxys
N HO Cl H
HN HO
Rx-ID: 541111 View in Reaxys 184/224 Yield Conditions & References With methanol, platinum, Hydrogenation Tilford; Van Campen; Journal of the American Chemical Society; vol. 76; (1954); p. 2431,2435, 2438; Journal of the American Chemical Society; vol. 79; (1957); p. 6575 View in Reaxys
NH
O O
NH
O O
N H
Rx-ID: 859972 View in Reaxys 185/224 Yield Conditions & References With hydrogen, palladium on activated charcoal in methanol Scopes,D.I.C. et al.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1977); p. 2376 - 2385 View in Reaxys
NH
NH
N H
Rx-ID: 11794658 View in Reaxys 186/224 Yield Conditions & References Reaction Steps: 2 1: triethylamine / tetrahydrofuran / 30 C 2: 14 percent Spectr. / acetic acid; hydrogen / platinum(II) oxide monohydrate / ethanol / 24 h / 40 C / 45600 Torr
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With hydrogen, acetic acid, triethylamine, platinum (IV) oxide in tetrahydrofuran, ethanol Kurkin, A. V.; Sumtsova, E. A.; Yurovskaya, M. A.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 43; nb. 1; (2007); p. 34 - 40; Khimiya Geterotsiklicheskikh Soedinenii; nb. 1; (2007); p. 41 - 48 View in Reaxys
F O
F O
HN
Rx-ID: 19310393 View in Reaxys 187/224 Yield Conditions & References Reaction Steps: 2 1: 1.) H2, glacial AcOH, 2.) NaOH / 1.) PtO2 / 1.) 1 atm, 8 h, 2.) THF, 24 h 2: 31 percent / TFA / 20 h / Heating With sodium hydroxide, hydrogen, acetic acid, trifluoroacetic acid, platinum(IV) oxide Cain; Christos; Cook; Drummond; Gilligan; Johnson; Kergaye; McElroy; Rohrbach; Schmidt; Tam; Journal of Medicinal Chemistry; vol. 35; nb. 23; (1992); p. 4344 - 4361 View in Reaxys
N N N NH O F
HN N N NH O F
Rx-ID: 25411011 View in Reaxys 188/224 Yield Conditions & References 17 : 8-Fluoro-2,3,4,4a-Tetrahydro-3-[2-(4-Piperidinyl)Ethyl]-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One EXAMPLE 17 8-Fluoro-2,3,4,4a-Tetrahydro-3-[2-(4-Piperidinyl)Ethyl]-1H-Pyrazino[1,2-a]Quinoxalin-5(6H)-One From 3 g. of 8-fluoro-2,3,4,4a-tetrahydro-3-[2-(4-pyridinyl)ethyl]-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one treated in the same manner as Example 16, there was obtained 2.5 g. of product, the title compound as the dihydrochloride salt, m.p. 227-230 C. (from ethanol). Analysis for: C18 H25 FN4 O.2HCl.H2 O. Calculated: C, 49.88; H, 6.74; N, 12.93; Cl, 16.36. Found: C, 49.81; H, 6.48; N, 12.73; Cl, 6.10. Patent; American Home Products Corporation; US4203987; (1980); (A1) English View in Reaxys
N N
HN N
Rx-ID: 920536 View in Reaxys 189/224 Yield Conditions & References With hydrogen, platinum Heitmeier,D.E. et al.; Journal of Organic Chemistry; vol. 36; (1971); p. 1449 - 1455 View in Reaxys
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H N
O O O
Rx-ID: 953843 View in Reaxys 190/224 Yield Conditions & References With hydrogen, rhodium on alumina Nielsen,A.T. et al.; Journal of Organic Chemistry; vol. 29; (1964); p. 2898 - 2903 View in Reaxys
HO
HO
NH
Rx-ID: 277711 View in Reaxys 191/224 Yield Conditions & References With acetic acid, platinum, Hydrogenation Patent; Merrell Co.; US2804422; (1954) View in Reaxys Reaction Steps: 5 1: acetone / 20 C 2: sodium tetrahydroborate / methanol / 4 h / 20 C 3: cyclohexanol / 2 h / Reflux 4: potassium carbonate / chloroform / 20 C 5: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions With sodium tetrahydroborate, potassium carbonate, cyclohexanol in methanol, ethanol, chloroform, acetone Benaka Prasad, S. B.; Vinaya, K.; Ananda Kumar, C. S.; Rangappa, K. S.; Swarup, Sanjay; Medicinal Chemistry Research; vol. 19; nb. 3; (2010); p. 220 - 235 View in Reaxys
NH
O O S O
O O S O
Rx-ID: 9688194 View in Reaxys 192/224 Yield Conditions & References With hydrogen, palladium on activated charcoal Agai, Bela; Faigl, Ferenc; Proszenyak, Agnes; Vida, Laszlo; Tarkanyi, Gabor; European Journal of Organic Chemistry; nb. 17; (2004); p. 3623 - 3632 View in Reaxys
71/80
2013-11-08 02:44:35
H N
O NH NH O O O O O
O NH NH O O O
Rx-ID: 8591160 View in Reaxys 193/224 Yield Conditions & References With platinum(IV) oxide, hydrogen in ethanol, water, acetic acid, Catalytic hydrogenation Bergum, Peter W.; Brunck, Terence K.; Cohen, Cheryl R.; Goldman, Erick A.; Ho, Jonathan Z.; Levy, Odile E.; Nutt, Ruth F.; Reiner, John E.; Semple, J. Edward; Tamura, Susan Y.; Uong, Theresa H.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 8; (2000); p. 745 - 749 View in Reaxys
N O O O
HN O O O
Rx-ID: 9617722 View in Reaxys 194/224 Yield Conditions & References With hydrogen, acetic acid, platinum(IV) oxide Ishii, Noe; Kakefuda, Akio; Kubota, Hideki; Masuda, Noriyuki; Sakamoto, Shuichi; Tsukamoto, Shin-Ichi; Wada, Kouichi; Watanabe, Toshihiro; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 12; (2004); p. 3049 - 3052 View in Reaxys
F
HO O F F F HN
Rx-ID: 12209131 View in Reaxys 195/224 Yield Conditions & References Reaction Steps: 3 1.1: acetone / 16 h / Heating 2.1: NaBH4 / methanol / 16 h / Heating 2.2: H2; aq. HCl / Pd(OH)2 / ethanol 2.3: NaOH / dioxane With sodium tetrahydroborate in methanol, acetone Ladduwahetty, Tammy; Boase, Amanda L.; Mitchinson, Andrew; Quin, Caroline; Patel, Smita; Chapman, Kerry; MacLeod, Angus M.; Bioorganic & Medicinal Chemistry Letters; vol. 16; nb. 12; (2006); p. 3201 - 3204 View in Reaxys
HN O
N O O H N F
F NH
F F
72/80
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Yield
Conditions & References With Adam's catalyst, hydrogen, acetic acid in ethanol Benbow, John W.; Andrews, Kim A.; Aubrecht, Jiri; Beebe, David; Boyer, David; Doran, Shawn; Homiski, Michael; Hui, Yu; McPherson, Kirk; Parker, Janice C.; Treadway, Judith; VanVolkenberg, Maria; Zembrowski, William J.; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 8; (2009); p. 2220 - 2223 View in Reaxys
H N
OH Cl H
OH
Rx-ID: 540864 View in Reaxys 197/224 Yield Conditions & References With ethanol, platinum, Hydrogenation Patent; Merrell Co.; US2832786; (1956) View in Reaxys McCarty et al.; Journal of Organic Chemistry; vol. 26; (1961); p. 4084,4086 View in Reaxys With methanol, platinum, Hydrogenation Patent; Merrell Co.; US2832786; (1956) View in Reaxys McCarty et al.; Journal of Organic Chemistry; vol. 26; (1961); p. 4084,4086 View in Reaxys
H N
OH
Cl
OH
Rx-ID: 541955 View in Reaxys 198/224 Yield Conditions & References With methanol, platinum Patent; Merrell Co.; US2832786; (1956) View in Reaxys McCarty et al.; Journal of Organic Chemistry; vol. 26; (1961); p. 4084,4086 View in Reaxys With ethanol, platinum Patent; Merrell Co.; US2832786; (1956) View in Reaxys McCarty et al.; Journal of Organic Chemistry; vol. 26; (1961); p. 4084,4086 View in Reaxys
73/80
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H N
O HO O HO O
Rx-ID: 1449345 View in Reaxys 199/224 Yield Conditions & References With hydrogen, palladium on activated charcoal Nielsen,A.T.; Platt,E.N.; Journal of Heterocyclic Chemistry; vol. 6; (1969); p. 891 - 900 View in Reaxys
H N
Rx-ID: 90875 View in Reaxys 200/224 Yield Conditions & References With acetic acid, platinum, p= 2942.03Torr , Hydrogenation Chough; ; vol. <C> 8; (1959); p. 335,351; ; (1960); p. 13129 View in Reaxys
H N
Rx-ID: 144675 View in Reaxys 201/224 Yield Conditions & References With acetic acid, platinum, p= 2942.03Torr , Hydrogenation Chough; ; vol. <C> 8; (1959); p. 335,351; ; (1960); p. 13129 View in Reaxys
H N
Rx-ID: 1649879 View in Reaxys 202/224 Yield Conditions & References With hydrogen, sodium, palladium on activated charcoal, 1.) ethanol, reflux, Multistep reaction Adomenas, P.; Sirutkaitis, R.; Molecular Crystals and Liquid Crystals (1969-1991); vol. 124; (1985); p. 269 - 276 View in Reaxys
74/80
2013-11-08 02:44:35
H N
H N
H N
H N
Rx-ID: 1753159 View in Reaxys 206/224 Yield Conditions & References With hydrogen, sodium, palladium on activated charcoal, 1.) ethanol, reflux, Multistep reaction
75/80
2013-11-08 02:44:35
Adomenas, P.; Sirutkaitis, R.; Molecular Crystals and Liquid Crystals (1969-1991); vol. 124; (1985); p. 269 - 276 View in Reaxys
O N
N O O
N H
Rx-ID: 35348552 View in Reaxys 207/224 Yield Conditions & References Reaction Steps: 3 1: acetonitrile / 1 h / 80 C / |Inert atmosphere 2: sodium tetrahydroborate; sodium hydrogencarbonate / ethanol / 1.17 h / 0 - 20 C / |Inert atmosphere 3: hydrogen; palladium(II) oxide hydrate / ethanol / 96 h / 20 C / 2585.81 Torr / |Inert atmosphere With sodium tetrahydroborate, hydrogen, palladium(II) oxide hydrate, sodium hydrogencarbonate in ethanol, acetonitrile Patent; Connolly, Peter J.; Bian, Haiyan; Li, Xun; Liu, Li; Macielag, Mark J.; McDonnell, Mark E.; US2013/102584; (2013); (A1) English View in Reaxys
H N
Rx-ID: 158573 View in Reaxys 208/224 Yield Conditions & References With sodium, butan-1-ol, Hydrierung des Reaktionsprodukts an Platin in Essigsaeure Sury; Hoffmann; Helvetica Chimica Acta; vol. 37; (1954); p. 2133,2141; Helvetica Chimica Acta; vol. 38; (1955); p. 728,735 View in Reaxys
H N
Br
Br
Rx-ID: 538824 View in Reaxys 209/224 Yield Conditions & References With water, platinum, Hydration Lukes; Galik; Collection of Czechoslovak Chemical Communications; vol. 21; (1956); p. 620,623 View in Reaxys
H N
Br
HO HO
HO HO
Rx-ID: 539029 View in Reaxys 210/224 Yield Conditions & References With water, platinum, Hydrogenation
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Lukes; Ernest; Collection of Czechoslovak Chemical Communications; vol. 14; (1949); p. 665,672 View in Reaxys
H N
H N
Rx-ID: 26950 View in Reaxys 211/224 Yield Conditions & References With sulfuric acid, Electrolysis Ferles; Collection of Czechoslovak Chemical Communications; vol. 24; (1959); p. 1029,1031, 1033 View in Reaxys
H N
Rx-ID: 149213 View in Reaxys 212/224 Yield Conditions & References With ethanol, sodium Ames; Bowman; Journal of the Chemical Society; (1952); p. 1057,1062 View in Reaxys
H N
Rx-ID: 159154 View in Reaxys 213/224 Yield Conditions & References With acetic acid, platinum, Hydrogenation Chough; ; vol. <C> 8; (1959); p. 335,350; ; (1960); p. 13129 View in Reaxys
H N
O O O O O
Rx-ID: 350535 View in Reaxys 214/224 Yield Conditions & References With hydrogenchloride, platinum, Hydrogenation Rubzow et al.; Zhurnal Obshchei Khimii; vol. 26; (1956); p. 445,446; engl. Ausg. S. 469, 470
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2013-11-08 02:44:35
View in Reaxys
HN
HO
HO
Rx-ID: 353926 View in Reaxys 215/224 Yield Conditions & References With water, acetic acid, platinum, Hydrogenation Patent; Merrell Co.; US2832786; (1956) View in Reaxys
O O O N H N
O O O N H NH
Rx-ID: 402401 View in Reaxys 216/224 Yield Conditions & References With ethanol, nickel, anschliessend Hydrieren an Platin unter Zusatz von Essigsaeure Barash; Osbond; Journal of the Chemical Society; (1959); p. 2157,2163 View in Reaxys
H N O O
O O
O O
O O
Rx-ID: 467730 View in Reaxys 217/224 Yield Conditions & References With hydrogenchloride, platinum, Hydrogenation Rubzow et al.; Zhurnal Obshchei Khimii; vol. 24; (1954); p. 2059,2061; engl. Ausg. S. 2025, 2027 View in Reaxys
Cl
Cl
N O
HN O
Rx-ID: 922692 View in Reaxys 218/224 Yield Conditions & References (i) Raney-Ni, EtOH, (ii) H2, PtO2, AcOH, Multistep reaction McCaustland,D.J. et al.; Journal of Medicinal Chemistry; vol. 17; nb. 9; (1974); p. 993 - 1000 View in Reaxys
78/80
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N H
N H
Rx-ID: 80993 View in Reaxys 219/224 Yield Conditions & References With hydrogenchloride, platinum, Hydrogenation Veer; Goldschmidt; Recueil des Travaux Chimiques des Pays-Bas; vol. 65; (1946); p. 793 View in Reaxys
H N
OH
H N
sodium
Rx-ID: 5411837 View in Reaxys 220/224 Yield Conditions & References Wawzonek et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2894 View in Reaxys Lukes; Ferles; Collection of Czechoslovak Chemical Communications; vol. 20; (1955); p. 1227,1232 View in Reaxys
N
OH
H N
sodium
Rx-ID: 5404498 View in Reaxys 221/224 Yield Conditions & References Ladenburg; Justus Liebigs Annalen der Chemie; vol. 247; (1888); p. 79 View in Reaxys
N OH HO S OO
H N
H N
lead-cathode
Rx-ID: 5410272 View in Reaxys 222/224 Yield Conditions & References elektrochemische Reduktion Ferles; Collection of Czechoslovak Chemical Communications; vol. 24; (1959); p. 1029,1031, 1033 View in Reaxys
H N
OH
H N
sodium
Rx-ID: 5410273 View in Reaxys 223/224 Yield Conditions & References elektrochemische Reduktion Ferles; Collection of Czechoslovak Chemical Communications; vol. 24; (1959); p. 1029,1031, 1033 View in Reaxys
79/80
2013-11-08 02:44:35
OH
sodium
N H
4-benzyl-piperideine
Rx-ID: 5675846 View in Reaxys 224/224 Yield Conditions & References Tschitschibabin; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 34; (1902); p. 511; Chem. Zentralbl.; vol. 73; nb. II; (1902); p. 597 View in Reaxys
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224 reactions in 2013-11-08 02h:39m:04s (EST) Reaxys

Search as: Ignore stereo, No salts, No mixtures, No isotopes, No charges, No radicals

Rx-ID: 27873873 View in Reaxys 13/224

3.46-3.77 (m, 7H, 3xCH2-N, CH-

Rx-ID: 9687977 View in Reaxys 24/224

Rx-ID: 2774804 View in Reaxys 28/224

Rx-ID: 10701048 View in Reaxys 40/224

Rx-ID: 2480560 View in Reaxys 149/224

Rx-ID: 29044757 View in Reaxys 196/224

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