Sodium hydride → tert-Butyl 4-cyano-4-(3-fluorophenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-fluorophenylacetonitrile (200 mg, 1.48 mmol) and tert-butyl bis(2-chloroethyl)carbamate (358 mg, 1.48 mmol) was dissolved in 14.8 mL of anhydrous DMSO. The reaction was purged with a stream of nitrogen and cooled to 18° C. To this reaction was added sodium hydride (358 mg, 1.48 mmol), which was then warmed to ambient temperature and stirred for 2 hours. The reaction was warmed to 50° C. and stirred for 17 hours. The mixture was diluted with dichloromethane (40 mL), washed with water (3×40 mL), and partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-20% EtOAc in hexanes. Collection of product containing fractions and removal of solvent yielded tert-butyl 4-cyano-4-(3-fluorophenyl)piperidine-1-carboxylate.

Provenance & Evidence