Peracetic Acid → 3-Bromo-6-chloro-2-fluorophenol

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-bromo-4-chloro-2-fluorobenzene (5 g, 23.87 mmol) in tetrahydrofuran (40 mL) was cooled to −78° C. was added LDA, 2M in THF/heptane/ethylbenzene (14.92 mL, 29.8 mmol) dropwise and the reaction mixture was stirred at this temperature for 30 min. The solution was allowed to warm to −20° C. and stirred for 30 min. The reaction was cooled to −78° C. and trimethyl borate (3.47 mL, 31.0 mmol) dissolved in THF (5 mL) was added dropwise and the reaction mixture was warmed to −20° C. and stirred for 1 h. The reaction mixture was cooled to −78° C. and peracetic acid (16 mL, 84 mmol) was added dropwise and the mixture allowed to warm to rt and stirred for 12 h. The reaction mixture was cooled to 0° C. and quenched with 5% aqueous ammonium chloride and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (50 mL). The organic layer was dried over sodium sulphate and concentrated under reduced pressure to yield 3-bromo-6-chloro-2-fluorophenol (4.99 g, 18.25 mmol, 76% yield) as yellow oil. LCMS (ESI) m/e 225.1 [(M+H)+, calcd for C6H4BrClFO 224.9]; LC/MS retention time (method G): tR=0.87 min.

Provenance & Evidence