Ammonia → (R)-piperidine-3-carboxamide

Participants

Reaction Steps

To 14.7 g (93.5 mmol) of (R)-ethyl nipecotate in a 300 ml round-bottomed flask were added 200 ml of concentrated aqueous ammonia at room temperature, and the mixture was allowed to stand for 3 days at room temperature. The reaction mixture was distilled off at a water bath temperature of lower than 40° C. to obtain (R)-nipecotamide as a pale yellow oil. To this were added 100 ml of methylene chloride and 50 ml of ethanol at room temperature, and 15.6 ml (1.2 eg.) of triethylamine were added while cooling with ice. To this reaction mixture were gradually added dropwise 11.1 ml (1 eg.) of benzyl bromide under cooling with ice. After dropwise addition, the mixture was stirred for 10 minutes under cooling with ice and further for 4 hours after returned to room temperature, which was allowed to stand overnight. The reaction mixture was distilled off under reduced pressure and the residue obtained was dissolved into 200 ml of methylene chloride, which was washed with 1N sodium hydroxide and saturated aqueous solution of sodium chloride in turn. The aqueous layer was extracted with methylene chloride (50 ml×3) and, after washed with saturated aqueous solution of sodium chloride, these were combined with previous organic layer and dried over anhydrous sodium sulfate. Solvent was distilled off under reduced pressure and the residue thus obtained was recrystallized to obtain 8.61 g (yield 42 %) of title compound.

Provenance & Evidence