Diisopropylamine → 1-(5-Bromo-2-fluorophenyl)-2,2-difluoroethanone

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Reaction Conditions

Reaction Steps

A solution of diisopropylamine (12.7 g, 17.9 ml, 126 mmol) and tetrahydrofuran (375 ml) was cooled to −78° C. and n-BuLi (1.6 M in hexane) (78.6 ml, 126 mmol) was added dropwise. After stirring for 10 min commercially available 1-bromo-4-fluorobenzene {CAS[460-00-4]} (20 g, 12.4 ml, 114 mmol) was added dropwise at max. −60° C. Stirring was continued at −70° C. for 2.5 hours. Then ethyl difluoroacetate (17.0 g, 13.7 ml, 137 mmol) was added dropwise and the mixture was warmed to −10° C. and then quenched by pouring the mixture onto 1 M HCl. The mixture was extracted twice with ethyl acetate, dried over sodium sulphate, filtered and evaporated to give a yellow liquid (34 g; 118%). The residue was chromatographed on 200 g silica gel with cyclohexane/ethyl acetate 3:1 to give 1-(5-bromo-2-fluorophenyl)-2,2-difluoroethanone (26.5 g, 105 mmol, 91.6% yield) as a yellow liquid. MS (EI): m/z=252.0 [M]+ and 254.0 [M+2]+.

Provenance & Evidence