Sodium hydride → 6-Chloro-2-(2,2-difluoro-ethoxy)-nicotinamide

Participants

Reaction Steps

2,2-Difluoroethanol (3.51 mL, 55.5 mmol) was added dropwise over 30 minutes to a suspension of NaH (2.22 g, 60% w/w dispersion in oil) in 1,2-dimethoxyethane (40.0 mL) at 14° C. and stirred for 1 hour. A portion of this solution (25 mL, 35 mmol) was added dropwise over 10 minutes to a solution of 2,6-dichloro-nicotinamide (5.30 g, 27.7 mmol) in dimethylformamide (40 mL) at 14° C. The resultant suspension was stirred for an additional 1 hour at 14° C., diluted with water (600 mL) and extracted with EtOAc (3×400 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated to give title compound as a light orange solid (6.39 g, 97%). This was used without further purification.

Provenance & Evidence