tert-Butyl chloroacetate → t-Butyl 3,5-difluoro4-nitrophenylacetate

Participants

Reaction Conditions

Reaction Steps

A mixture of potassium tert-butoxide (248 g) in NMP (2000 ml) was cooled under nitrogen to −20° C. A mixture of 2,6-difluoronitrobenzene (10 g) and tert-butylchloroacetate (160 g) in NMP (2000 ml) was added slowly at −10° C. to −20° C. over 1.5 hours. After 30 minutes, a further portion of potassium tert-butoxide (88 g) was added. The reaction mass was quenched into 1600 ml of 2M HCl and 1 kg crushed ice, then 2000 ml hexane was added and the mixture stirred for 10 minutes. The layers were separated and the aqueous layer was extracted with hexane (2×1500 ml). The combined hexane layers were washed with saturated brine (2×1000 ml), then dried over anhydrous sodium sulphate, then filtered and washed with 200 ml hexane. The solution was then evaporated to give the title compound as a brown liquid (152 g).

Provenance & Evidence