Triethylamine → trans-N-cyanomethyl-2-hydroxymethyl-cyclohexanecarboxamide

Participants

Reaction Steps

trans-1,2-Cyclohexanedicarboxylic anhydride (19.64 g, 127 mmol) and aminoacetonitrile hydrochloride (12.05 g, 130 mmol) were weighed into a dry 500 mL flask fitted with a stir bar and nitrogen inlet. After adding anhydrous dichloromethane (200 mL), triethylamine (39.1 mL, 281 mmol) was added at a moderate rate, allowing the reaction to warm the solution to near boiling point. The reaction mixture was allowed to cool to room temperature over 1 h, after which it was cooled to −10° C. and isobutyl chloroformate (18.2 mL, 140 mmol) was added dropwise, keeping the reaction temperature below 0° C. After the addition was complete, the reaction was allowed to warm to room temperature. After 1 h, the reaction mixture was diluted with anhydrous tetrahydrofuran (200 mL) and stired at 0° C. for 1 h. The precipitate were filtered and washed with cold anhydrous tetrahydrofuran (100 mL). The filtrate was taken in a 1000 mL flask and fitted with a stir bar and a 50 mL addition funnel. The solution was cooled to −25° C. and a solution of sodium borohydride (6.90 g, 182 mmol) in water (30 mL) was added at a slow dropping rate, keeping the reaction temperature below −15° C. After the addition was complete, the reaction mixture was stirred for 1 h between −20° C. and −10° C. After warming the reaction mixture to warm to room temperature and stirring for an additional 1 h, anhydrous magnesium sulfate was added and stirring was continured for additional 30 min, filtered and the filtrate was concentrated on a rotary evaporator. Product was purified from the residue by chromatography using 9:1 dichloromethane:methanol eluent. The product fractions were concentrated on a rotary evaporator and dried under high vacuum to give trans-N-cyanomethyl-2-hydroxymethyl-cyclohexanecarboxamide as a white solid.

Provenance & Evidence