Potassium carbonate (5.870 g, 42.47 mmol) was slowly added to a stirred solution of 4-bromo-5-fluoro-2-nitrobenzoic acid (Ark Pharm, 5.387 g, 20.40 mmol) in N,N-dimethylformamide (DMF, 80.0 mL) at 0 °C, followed by dropwise addition of iodomethane (8.789 g, 61.92 mmol). The reaction mixture was stirred at 0 °C for 15 min and then gradually warmed up to 40 °C and maintained for 2 hours. After completion of the reaction, the mixture was filtered and concentrated. The concentrated residue was dissolved in ethyl acetate (EtOAc, 150 mL), washed sequentially with water (2 x 100 mL) and saturated brine (100 mL), and the organic phase was dried with anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure to remove the solvent. The crude product obtained was purified by fast column chromatography on silica gel with the eluent being hexane solution of 0-50% ethyl acetate to give methyl 4-bromo-5-fluoro-2-nitrobenzoate as a light yellow oil (5.348 g, 94% yield). Liquid chromatography-mass spectrometry (LCMS) analysis: theoretically calculated value for C8H6BrFNO4 ([M+H]+): m/z = 277.9; no ionization was observed.
