Water → 2-Bromo-3-chloro-4-fluorobenzoic acid

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Reaction Conditions

Reaction Steps

n-Butyl lithium (25M solution, 76 ml) was added to a stirred solution of diisopropylamine (28 ml) in dry tetrahydrofuran (THF) at −75° C., and maintained at −30° C. for a further 1 hour, to produce lithium diisopropylamide (LDA). After re-cooling to −75° C., a solution of 3 -chloro-4-fluorobenzoic acid (14.4 g) in dry THF was added over 1 hour, and stirring was continued overnight at −75° C. A solution of 1,2-dibromotetrachloroethane (42.77 g) in dry THF was then added over 20 minutes, stirring was continued for 2 hours at −70° C. then at room temperature for 4 hours. Water was added, the organic and aqueous phases were separated and the aqueous phase was washed with ether, then acidified with hydrochloric acid solution and extracted with dichloromethane. The dichloromethane extract was dried (anhydrous magnesium sulphate) and the solvent evaporated to give 2-bromo-3-chloro-4-fluorobenzoic acid (19.54 g) as a beige solid, NMR (DMSO-D6) 7.55(t,1H), 7.75(dd,1H), 13.8(brs,1H).

Provenance & Evidence