methyl 1-methylpiperidine-4-carboxylate

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: To a deep cold (below -70° C.) solution of methyl 1-methylisonipecotate (15.7 g. 0.1 mol) in 500 mL of hexane was added, dropwise over 1 hr, 100 mL of 1N diisobutylaluminum hydride (DIBAL-H) in hexane. The solution was stirred for 1.5 h, and 20 mL of saturated aqueous ammonium chloride was very slowly added. The reaction mixture was gradually allowed to come to ambient temperature and stirring was continued for an additional hour. To the reaction mixture was added 10 mL of saturated aqueous sodium bicarbonate and the organic layer was decanted. The aqueous layer was extracted with methylene chloride (200 mL×3) and then with ether (200 mL×3). The combined extracts were dried with magnesium sulfate and evaporated to give 10 g (79%) of a pale yellow oil (crude). The crude aldehyde was used for further reaction without purification. to come to ambient temperature stirring was continued for an additional hour the organic layer was decanted The aqueous layer was extracted with methylene chloride (200 mL×3) The combined extracts were dried with magnesium sulfate evaporated

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-methylisonipecotic acid hydrochloride (178.64 g, 1 mol) in 350 mL of methanol (8 equivalents) was added, dropwise with stirring and cooling (ice-salt bath) to -10° C., 112.8 mL (1.55 equivalents) of thionyl chloride. After completion of the addition (1 hour), the ice-salt bath was removed and the temperature allowed to rise to 40° C. and held at this point for 2 hours. The solution was brought to about pH 8 with sodium carbonate and extracted with methylene chloride. The methylene chloride solution was dried and evaporated to give 136.88 g (87%) of methyl 1-methylpiperidine-4-carboxylate as a clear liquid. The IR spectrum confirmed that the product was the methyl ester. After completion of the addition (1 hour) the ice-salt bath was removed to rise to 40° C. extracted with methylene chloride The methylene chloride solution was dried evaporated

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 25 mL sealed tube, methyl 1-methylpiperidine-4-carboxylate (0.2 g, 1.0 eq.) was dissolved in ethanol (5 mL) at RT. Hydrazine hydrate (0.127 g, 2 eq.) was introduced dropwise at RT and the reaction mixture was heated at 120° C. for 20 h. The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg) to afford the crude 1-methylpiperidine-4-carbohydrazide (0.145 g) which was used without further purification in the following step. In a 25 mL sealed tube The reaction mixture was concentrated under reduced pressure (40° C., 20 mm Hg)

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

実験手順: Dissolve isonipecotic acid methyl ester in formaldehyde (19.4 mL of a 37.5% solution in water, 262 mmol) and treat with formic acid (10.2 mL of a 90% solution, 240 mmol). Heat on a steam bath for 2 hours and evaporate the solvent in vacuo. Dissolve the residue in ethyl ether, dry (MgSO4), filter and evaporate the filtrate in vacuo. Purify by distillation under an argon atmosphere to give 1-methyl-4-piperidinecarboxylic acid, methyl ester as a clear colorless oil (bp 195°-205° C., 760 mm). Heat on a steam bath for 2 hours evaporate the solvent in vacuo Dissolve the residue in ethyl ether dry (MgSO4) filter evaporate the filtrate in vacuo Purify by distillation under an argon atmosphere

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

実験手順: To a deep cold (below -70° C.) solution of methyl 1-methylisonipecotate (15.7 g. 0.1 mol) in 500 mL of hexane was added, dropwise over 1 hr, 100 mL of 1N diisobutylaluminum hydride (DIBAL-H) in hexane. The solution was stirred for 1.5 h, and 20 mL of saturated aqueous ammonium chloride was very slowly added. The reaction mixture was gradually allowed to come to ambient temperature and stirring was continued for an additional hour. To the reaction mixture was added 10 mL of saturated aqueous sodium bicarbonate and the organic layer was decanted. The aqueous layer was extracted with methylene chloride (200 mL×3) and then with ether (200 mL×3). The combined extracts were dried with magnesium sulfate and evaporated to give 10 g (79%) of a pale yellow oil (crude). The crude aldehyde was used for further reaction without purification. to come to ambient temperature stirring was continued for an additional hour the organic layer was decanted The aqueous layer was extracted with methylene chloride (200 mL×3) The combined extracts were dried with magnesium sulfate evaporated

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-methylisonipecotic acid hydrochloride (178.64 g, 1 mol) in 350 mL of methanol (8 equivalents) was added, dropwise with stirring and cooling (ice-salt bath) to -10° C., 112.8 mL (1.55 equivalents) of thionyl chloride. After completion of the addition (1 hour), the ice-salt bath was removed and the temperature allowed to rise to 40° C. and held at this point for 2 hours. The solution was brought to about pH 8 with sodium carbonate and extracted with methylene chloride. The methylene chloride solution was dried and evaporated to give 136.88 g (87%) of methyl 1-methylpiperidine-4-carboxylate as a clear liquid. The IR spectrum confirmed that the product was the methyl ester. After completion of the addition (1 hour) the ice-salt bath was removed to rise to 40° C. extracted with methylene chloride The methylene chloride solution was dried evaporated