To a solution of methyl 5-bromo-2-hydroxybenzoate (409 mg, 1.77 mmol) in anhydrous DMF (5 mL) was sequentially added potassium carbonate (367 mg, 2.67 mmol) and ethyl 2-bromo-2,2-difluoroacetate (280 μL, 2.13 mmol). The reaction mixture was stirred at 80 °C for 24 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with ether (10 mL) and washed sequentially with water (10 mL), 10% aqueous hydrochloric acid solution (10 mL), water (10 mL) and saturated saline (10 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (elution gradient: n-hexane to n-hexane/ethyl acetate=2:1, v/v) to afford methyl 5-bromo-2-(difluoromethoxy)benzoate as a yellow oil (250 mg, 50% yield).
