3-Fluoro-5-bromophenol

461-96-1

433939-27-6

General procedure for the synthesis of 3-bromo-5-fluorophenol from 3,5-difluorobromobenzene: potassium tert-butoxide (76.6 g, 0.682 mol) was added to a solution of 1-bromo-3,5-difluorobenzene (30.6 mL, 0.266 mol) and 2-(methanesulfonyl)ethanol (66 g, 0.531 mol) in dimethylsulfoxide (DMSO, 240 mL) and the reaction was carried out at 0 °C. The reaction mixture was stirred at room temperature for 3 h, followed by slow quenching with 4 N hydrochloric acid to pH < 1. The reaction mixture was extracted several times with ether (Et2O, 12 L) until no product was detected in the aqueous phase. The ether phase was concentrated under reduced pressure to one-third of the original volume and then washed with 1N sodium hydroxide (NaOH, 12 L). After adjusting the sodium hydroxide solution to pH=3, it was again extracted with ether until no product was detected in the aqueous phase. The ether phases were combined, the solvents were evaporated under reduced pressure, and the residue was purified by alumina (Al2O3) column chromatography using ether as eluent to afford 3-bromo-5-fluorophenol as a colorless oil (48 g, 94% yield). The product was analyzed by LC-MS showing the molecular ion peak m/z 190.33 ([M+H]+); the analytical HPLC retention time was 2.26 min (mobile phase: 0-100% acetonitrile/water with 0.1% trifluoroacetic acid, run time 4 min); 1H NMR (400 MHz, CD3OD) δ ppm 6.88-6.64 (m, 2H), and 6.58-6.30 (m, 1H), 4.99 (s, 1H).