Sodium hydride → 4-(2,2-Difluoropropoxyl)pyrimidine-5-carbonitrile

Participants

Reaction Steps

To a suspension of sodium hydride (60% dispersed in mineral oil, 315 mg, 7.88 mmol) in THF (20 mL) was added 2,2-difluoropropan-1-ol (757 mg, 7.88 mmol) at 0° C. and the resulting mixture was stirred for 1 h. Then 4-chloropyrimidine-5-carbonitrile (1.00 g, 7.16 mmol) was added in portions and the mixture was stirred at room temperature for 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (500 mL×2). The combined organic layers were dried and concentrated and the residue was purified by silica gel chromatography column (12% ethyl acetate in petroleum ether) to afford the title compound (850 mg, 4.27 mmol, 58% yield) as a yellow solid. MS (ESI) m/z 200.0 [M+H]+.

Provenance & Evidence