Methyl iodide → 1-Bromo-4-chloro-2-fluoro-3-methoxybenzene

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 3-bromo-6-chloro-2-fluorophenol (4.2 g, 18.63 mmol) in acetonitrile (35 mL) was added potassium carbonate (5.15 g, 37.3 mmol) followed by methyl iodide (2.330 mL, 37.3 mmol) dropwise at rt. The reaction mixture was heated to 85° C. for 3 h. After cooling, the volatiles were concentrated under reduced pressure and the residue was diluted with water (50 mL) and extracted with ethyl acetate (2×80 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (4 g, 16.7 mmol, 90% crude yield) as a brown solid. The material was carried forward without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 7.2 (m, 1H), 7.04 (m, 1H), 3.98 (s, 3H).

Provenance & Evidence