Benzonitrile, 4-bromo- → 4-(1-Hydroxycyclobutyl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A 500 mL flask was charged with 10.8 g (59.4 mmol) 4-bromo-benzonitrile and 150 mL anhydrous THF. The solution was cooled to −78° C. and 26.1 mL (65.3 mmol) 2.5M n-butyl lithium was added dropwise. The reaction mixture was stirred at −78° C. for an additional 10 minutes, then 5.0 g (71.3 mmol)cyclobutanone was added dropwise. The reaction mixture was stirred for an additional 10 minutes at −78° C. then the bath was removed and the reaction stirred for an additional 1 hour. The material was poured into 300 mL water and extracted with ethyl acetate (3×100 mL). The combined organics were washed with water (2×100 mL), brine (1×100 mL), dried over Na2SO4 and concentrated to a light brown oil. The oil was chromatographed on a Biotage Flash 40S® silica column+SIM eluted with 10% ethyl acetate/90% hexanes to give 4.1 g of a light yellow oil.

Provenance & Evidence