methyl 4-hydroxypiperidine-4-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-hydroxypiperidine-4-carboxylate (0.4 g, 2.52 mmol) in EtOH (10 mL) was added DIPEA (2.2 mL, 12.57 mmol) and the solution stirred at rt for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.49 g, 2.52 mmol). The mixture was then heated up to 70° C. for 1 h. After completion of reaction (by TLC), solvent was evaporated and the crude residue purified over 100-200 M silica-gel using 10% EtOAc:hexane to obtain the desired product as a yellow solid (0.35 g, 44% yield). 1H NMR (DMSO-d6): δ 1.64 (m, 2H), 1.82 (m, 2H), 3.20 (m, 2H), 3.64 (s, 3H), 4.27 (m, 2H), 5.60 (s, 1H) and 8.44 (s, 2H). The mixture was then heated up to 70° C. for 1 h After completion of reaction (by TLC), solvent was evaporated the crude residue purified over 100-200 M silica-gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 1-benzyl-4-hydroxypiperidine-4-carboxylic acid (1.2 g, 5.1 mmol) in MeOH (15 mL) was added palladium hydroxide and the resulting mixture was stirred at rt for 6 h under H2 atmosphere. After completion (by TLC), the mixture was passed through celite and the filtrate evaporated under reduced pressure. The crude (1 g) residue was carried forward to the next step without further purification. MS: 160.18 [M+H]+. the filtrate evaporated under reduced pressure The crude (1 g) residue was carried forward to the next step without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-hydroxypiperidine-4-carboxylate (0.4 g, 2.52 mmol) in EtOH (10 mL) was added DIPEA (2.2 mL, 12.57 mmol) and the resulting solution stirred at rt for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.49 g, 2.52 mmol). The reaction mixture was then heated up to 70° C. for 1 h. After completion of reaction (by TLC), solvent was evaporated and the crude residue purified over 100-200 M silica-gel using 10% EtOAc:hexane to obtain the product as a yellow solid (0.35 g, 44% yield). 1H NMR (DMSO-d6): δ 1.64 (m, 2H), 1.82 (m, 2H), 3.20 (m, 2H), 3.64 (s, 3H), 4.27 (m, 2H), 5.60 (s, 1H) and 8.44 (s, 2H). The reaction mixture was then heated up to 70° C. for 1 h After completion of reaction (by TLC), solvent was evaporated the crude residue purified over 100-200 M silica-gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-hydroxypiperidine-4-carboxylate (0.4 g, 2.52 mmol) in EtOH (10 mL) was added DIPEA (2.2 mL, 12.57 mmol) and the resulting solution stirred at rt for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.49 g, 2.52 mmol). The reaction mixture was then heated up to 70° C. for 1 h. After completion of reaction (by TLC), solvent was evaporated and the crude residue purified over 100-200 M silica-gel using 10% EtOAc:hexane to obtain the product as a yellow solid (0.35 g, 44% yield). 1H NMR (DMSO-d6): δ 1.64 (m, 2H), 1.82 (m, 2H), 3.20 (m, 2H), 3.64 (s, 3H), 4.27 (m, 2H), 5.60 (s, 1H) and 8.44 (s, 2H). The reaction mixture was then heated up to 70° C. for 1 h After completion of reaction (by TLC), solvent was evaporated the crude residue purified over 100-200 M silica-gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 1-benzyl-4-hydroxypiperidine-4-carboxylic acid (1.2 g, 5.10 mmol) in MeOH (15 mL) was added palladium hydroxide and the resulting mixture was stirred at rt for 6 h under H2 atmosphere. After completion of reaction (by TLC), the reaction was passed through celite and the filtrate evaporated under reduced pressure to give the desired product (1 g). MS: 160.18 [M+H]+. After completion of reaction (by TLC) the filtrate evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Hydroxy-4-piperidinecarboxylic acid hydrochloride salt (1 g, 5.1 mmol) was added to a 2% hydrochloric acid solution in methanol (25 mL) and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure to give the title compound as the hydrochloride salt (1 g, 92%) as a white solid. δH (400 MHz, DMSO-d6) 9.06 (broad, 2H), 5.89 (broad, 1H), 3.68 (m, 3H), 3.14 (m, 2H), 3.02 (m, 2H), 2.07 (m, 2H), 1.79 (m, 2H). The solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Hydroxy-4-piperidinecarboxylic acid hydrochloride salt (1 g, 5.1 mmol) was added to a 2% hydrochloric acid solution in methanol (25 mL) and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure to give the title compound as the hydrochloride salt (1 g, 92%) as a white solid. δH (400 MHz, DMSO-d6) 9.06 (broad, 2H), 5.89 (broad, 1H), 3.68 (m, 3H), 3.14 (m, 2H), 3.02 (m, 2H), 2.07 (m, 2H), 1.79 (m, 2H). The solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 1-benzyl-4-hydroxy-4-piperidinecarboxylate in methanol was treated with Pd(OH)2 (20% on carbon, 500 mg) under a hydrogen atmosphere. The mixture was allowed to stir at room temperature for 12 hours, filtered, and the filtrate was concentrated under reduced pressure. filtered the filtrate was concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 1-benzyl-4-hydroxy-4-piperidinecarboxylate in methanol was treated with Pd(OH)2 (20% on carbon, 500 mg) under a hydrogen atmosphere. The mixture was allowed to stir at room temperature for 12 hours, filtered, and the filtrate was concentrated under reduced pressure. filtered the filtrate was concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-hydroxypiperidine-4-carboxylate (0.4 g, 2.52 mmol) in EtOH (10 mL) was added DIPEA (2.2 mL, 12.57 mmol) and the solution stirred at rt for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.49 g, 2.52 mmol). The mixture was then heated up to 70° C. for 1 h. After completion of reaction (by TLC), solvent was evaporated and the crude residue purified over 100-200 M silica-gel using 10% EtOAc:hexane to obtain the desired product as a yellow solid (0.35 g, 44% yield). 1H NMR (DMSO-d6): δ 1.64 (m, 2H), 1.82 (m, 2H), 3.20 (m, 2H), 3.64 (s, 3H), 4.27 (m, 2H), 5.60 (s, 1H) and 8.44 (s, 2H). The mixture was then heated up to 70° C. for 1 h After completion of reaction (by TLC), solvent was evaporated the crude residue purified over 100-200 M silica-gel