Step 1: Synthesis of 4-bromo-2-fluoro-N-methylbenzamide
To a 100 mL round-bottomed flask were added 4-bromo-2-fluorobenzoic acid (3.0 g, 13.7 mmol), 2 M aqueous methylamine (34.3 mL, 68.5 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI, 6.6 g, 34.25 mmol), 1-hydroxybenzotriazole (HOBt, 2.8 g 20.6 mmol), N,N-diisopropylethylamine (DIPEA, appropriate amount) and N,N-dimethylformamide (DMF, 50 mL). The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the reaction was quenched by the addition of water (50 mL). The aqueous phase was separated and the organic phase was extracted with ethyl acetate (3 x 50 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent ethyl acetate/petroleum ether (1:3, v/v) to afford the title compound 4-bromo-2-fluoro-N-methylbenzamide as a white solid (2.34 g, 74% yield). Mass spectrum (MS): [M+H]+ 232.
