Methanol → Methyl 1-Methyl-4-piperidinecarboxylate

Participants

Reaction Steps

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.

Provenance & Evidence