Hydrochloric Acid → 1-(2-Chloro-5-fluoropyrimidin-4-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

A room temperature solution of 5-fluoro-2,4-dichloro-pyrimidine (20 g, 119.8 mmol) and (1-ethoxyethenyl)trimethylstannane (43.26 g, 119.8 mmol) in dimethylformamide (200 mL) is purged with nitrogen. Bis(triphenylphosphine)palladium(II) chloride (1.70 g, 2.40 mmol) is added and the resulting mixture is heated to 70° C. for 2 hours under nitrogen. The reaction is cooled to 50° C. and aqueous 5 N hydrogen chloride (100 mL) is added and stirred for 2 hours. The reaction is cooled and diluted with water (200 mL) and brine and extracted five times with diethyl ether. The combined organic layers are dried over sodium sulfate and concentrated under vacuum. The crude product is purified using silica gel column chromatography using a 5-50% gradient of ethyl acetate in hexanes to give the title compound (19.2 g, 92%). GC/MS (m/e): 174 and 176.

Provenance & Evidence