Hydrochloric Acid → 1,1-Dimethylethyl 4-cyano-4-(dimethylamino)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

500 ml (10 equiv.) of dimethylamine solution and 109.9 g (5 equiv.) of dimethylamine hydrochloride were added to a solution of 50 g (1 equiv.) of tert-butyloxycarbonyl-4-oxopiperidine in 100 ml of methanol, and the mixture was cooled to 5° C. 5 ml (0.1 equiv.) of hydrochloric acid were then added dropwise, over a period of 10 minutes, to the reaction mixture, and stirring was carried out for 60 minutes at room temperature. 48.9 g (3 equiv.) of potassium cyanide were added in portions to the reaction mixture, and stirring was carried out for 24 hours at room temperature. The progress of the reaction was monitored by thin-layer chromatography (50% EtOAc/hexane). When the reaction was complete, 150 ml of water were added to the reaction mixture, and extraction was carried out 3× with 100 ml of ethyl acetate. The combined organic phases were dried with Na2SO4. After removal of the solvent under reduced pressure, crude product was obtained and was recrystallized from hexane. 57 g (90%) of product were obtained in the form of a colourless solid.

Provenance & Evidence