Chlorodifluoromethane → 6-Bromo-3-difluoromethoxy-2,4-dimethyl-pyridine

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Reaction Steps

A three-necked round bottom flask (500 mL) equipped with dry ice condenser (−78° C., acetone/dry ice) was charged with a solution of 6-bromo-2,4-dimethyl-3-hydroxypyridine (7.2 g, 35.6 mmol) in i-propanol (100 mL) and aqueous sodium hydroxide solution (20%, 100 mL) was added. The reaction mixture was stirred vigorously at 40° C. for 5 hours while chlorodifluoromethane was bubbled continuously into the solution at a moderate rate. The reaction mixture was then cooled to room temperature and extracted with Et2O (3×100 mL). The combined extracts were washed with water (2×50 mL), dried over magnesium sulfate and concentrated in vacuo. Purification of the crude mixture by flash column chromatography using 5% ethyl acetate in hexane afforded the title compound (5.4 g, 60%).

Provenance & Evidence