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) cooled to −78° C. was added LDA (14.92 mL, 29.8 mmol) dropwise. The reaction mixture was stirred at this temperature for 30 min. then allowed to warm to −20° C. and stirred for 30 min. The reaction was then cooled to −78° C. and trimethyl borate (3.47 mL, 31.0 mmol) dissolved in THF (5 mL) was added dropwise. The reaction mixture was warmed to −20° C. and stirred for 1 h. The reaction mixture was then cooled to −78° C. and peracetic acid (16 mL, 84 mmol) as slowly added dropwise. The mixture was allowed to warm to rt and stirred for 12 h. The reaction mixture was again cooled to 0° C. and quenched with 5% ammonium chloride The solution was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-bromo-6-chloro-2-fluorophenol (4.99 g, 18.25 mmol, 76% crude yield) as a yellow oil. The material was carried forward without further purification. LC/MS (ESI) m/e 225.1 [(M+H)+, calcd for C6H4BrClFO 224.9]; LC/MS retention time (method E): tR=0.87 min.

Provenance & Evidence