tert-butyl N-(1-benzylpiperidin-4-yl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: Compound 79 (4.55 g, 15.7 mmol), 10% palladium on carbon (400 mg), and ethanol (100 mL) were combined and hydrogenated in a Parr jar at 63psi for 3d. The mixture was filtrated through celite, followed by removal of the solvent in vacuo to afford 2.87 g (14.4 mmol, 91.4%) of Compound 80. The mixture was filtrated through celite followed by removal of the solvent in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

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: 6 g of Pd/C (10%) are added to a solution of 0.224 mol of tert-butyl 1-benzyl-4-piperidinylcarbamate in 800 ml of anhydrous ethanol. The reaction mixture is placed under a hydrogen pressure of 4 bars, at 50° C., for 48 hours, and then filtered over Celite and concentrated under reduced pressure, enabling the expected product to be isolated. filtered over Celite concentrated under reduced pressure to be isolated

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

実験手順: 6 g of Pd/C (10%) are added to a solution of 0.224 mol of tert-butyl 1-benzyl-4-piperidinylcarbamate in 800 ml of anhydrous ethanol. The reaction mixture is placed under a hydrogen pressure of 4 bars, at 50° C., for 48 hours, and then filtered over Celite and concentrated under reduced pressure, enabling the expected product to be isolated. filtered over Celite concentrated under reduced pressure to be isolated

反応条件: temp:2.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude solution containing 130 g of 4-(t-butoxycarbonylamino)-1-benzylpiperidine (0.448 mol) was hydrogenated at 45 psi, room temperature in the presence of 10% Pd/C (52 g, 50% wet) and stopped when theoretical amount of H2 was consumed (23.5 h, TLC). The mixture was filtered from the catalyst and the cake was washed with ethanol (500 mL). The filtrate was concentrated to about 100 mL, redissolved in ethanol and reconcentrated. The mixture was solvent switched to heptane (200 mL final volume) and cooled to 2° C. The slurry was filtered and the solid was washed with heptane (200 mL). The solid was dried in a vacuum oven overnight to give 84 g of the title compound as a white crystalline solid. was consumed (23.5 h, TLC) The mixture was filtered from the catalyst the cake was washed with ethanol (500 mL) The filtrate was concentrated to about 100 mL redissolved in ethanol The slurry was filtered the solid was washed with heptane (200 mL) The solid was dried in a vacuum oven overnight

反応条件: temp:2.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The crude solution containing 130 g of 4-(t-butoxycarbonylamino)-1-benzylpiperidine (0.448 mol) was hydrogenated at 45 psi, room temperature in the presence of 10% Pd/C (52 g, 50% wet) and stopped when theoretical amount of H2 was consumed (23.5 h, TLC). The mixture was filtered from the catalyst and the cake was washed with ethanol (500 mL). The filtrate was concentrated to about 100 mL, redissolved in ethanol and reconcentrated. The mixture was solvent switched to heptane (200 mL final volume) and cooled to 2° C. The slurry was filtered and the solid was washed with heptane (200 mL). The solid was dried in a vacuum oven overnight to give 84 g of the title compound as a white crystalline solid. was consumed (23.5 h, TLC) The mixture was filtered from the catalyst the cake was washed with ethanol (500 mL) The filtrate was concentrated to about 100 mL redissolved in ethanol The slurry was filtered the solid was washed with heptane (200 mL) The solid was dried in a vacuum oven overnight

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

実験手順: To a chilled solution of 1-benzyl-4-tert-butoxycarbonylaminopiperidine (6.8 g, 23.4 mmol) in DMF (200 mL) was added sodium hydride (0.6 g, 60% dispersion in mineral oil). After 30 min, 1,7-dibromoheptane was added (12 mL) and the reaction mixture was stirred for 24 h. Another portion of sodium hydride (0.6 g, 60% dispersion in mineral oil) was added and the reaction mixture was stirred for 18 h. The DMF was removed in vacuo and the residue extracted with dichloromethane and 1 N HCl (3×). The organic phase was washed with saturated brine, dried over sodium sulfate, filtered and concentrated to give 18.5 g of the crude intermediate. This crude product was purified by silica gel column chromatography, eluting with 1% methanol in dichloromethane. The appropriate fractions were combined and concentrated to afford 4.7 g of the title intermediate (85% pure by HPLC, MS and NMR), which was used without further purification. the reaction mixture was stirred for 18 h The DMF was removed in vacuo the residue extracted with dichloromethane and 1 N HCl (3×) The organic phase was washed with saturated brine dried over sodium sulfate filtered concentrated to give 18.5 g of the crude intermediate This crude product was purified by silica gel column chromatography eluting with 1% methanol in dichloromethane concentrated

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

実験手順: To a chilled solution of 1-benzyl-4-tert-butoxycarbonylaminopiperidine (6.8 g, 23.4 mmol) in DMF (200 mL) was added sodium hydride (0.6 g, 60% dispersion in mineral oil). After 30 min, 1,7-dibromoheptane was added (12 mL) and the reaction mixture was stirred for 24 h. Another portion of sodium hydride (0.6 g, 60% dispersion in mineral oil) was added and the reaction mixture was stirred for 18 h. The DMF was removed in vacuo and the residue extracted with dichloromethane and 1 N HCl (3×). The organic phase was washed with saturated brine, dried over sodium sulfate, filtered and concentrated to give 18.5 g of the crude intermediate. This crude product was purified by silica gel column chromatography, eluting with 1% methanol in dichloromethane. The appropriate fractions were combined and concentrated to afford 4.7 g of the title intermediate (85% pure by HPLC, MS and NMR), which was used without further purification. the reaction mixture was stirred for 18 h The DMF was removed in vacuo the residue extracted with dichloromethane and 1 N HCl (3×) The organic phase was washed with saturated brine dried over sodium sulfate filtered concentrated to give 18.5 g of the crude intermediate This crude product was purified by silica gel column chromatography eluting with 1% methanol in dichloromethane concentrated