1206980-28-0

41288-96-4

1885-46-7

1206980-28-0

GENERAL METHOD: To a vigorously stirred solution of 2-chloro-5-hydroxypyridine (0.13 g, 1.0 mmol) in acetonitrile (2 mL) was slowly added an aqueous solution of 6 M potassium hydroxide (2 mL) at room temperature. Subsequently, difluoromethyl trifluoromethanesulfonate (0.38 mL, 3.0 mmol, 3 eq.) was added dropwise to the reaction mixture while the reaction temperature was controlled by a water bath to maintain room temperature (note that the reaction is exothermic). Stirring of the reaction mixture was continued for 30 minutes. Upon completion of the reaction, the mixture was diluted with distilled water (20 mL) and extracted sequentially with ether (2 × 10 mL) and ethyl acetate (3 × 10 mL). All organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using a gradient elution of pentane/diethyl ether (100:0 to 70:30, v/v) to give pure 2-chloro-5-difluoromethoxypyridine.