Synthesis of 1-(5-bromo-2-fluorophenyl)ethanone (15): To a stirred solution of 5-bromo-2-fluoro-N-methoxy-N-methylbenzamide (14) (106 g, 404 mmol) in anhydrous tetrahydrofuran (THF) (1.7 L) was slowly added, under nitrogen protection and at 0 °C, an ether solution of methylmagnesium bromide (3.0 M, 270 mL, 808 (3.0 M, 270 mL, 808 mmol). After addition, the reaction was continued to be stirred at 0 °C for 6.5 hours. After completion of the reaction, the reaction solution was slowly poured into 2N hydrochloric acid (1 L) and gradually warmed to room temperature. The reaction mixture was extracted with ethyl acetate (2 x 1 L). The organic phases were combined, washed sequentially with saturated aqueous sodium bicarbonate (500 mL) and brine (500 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford the target product 15 (85.2 g, 97% yield) as an orange oil. The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 7.98 (dd, J = 6.4, 2.6 Hz, 1H), 7.61 (ddd, J = 8.7, 4.3, 2.6 Hz, 1H), 7.05 (dd, J = 10.4, 8.7 Hz, 1H), 2.64 (d, J = 4.9 Hz, 3H); ESI MS m/ z 217 [M + H]+.
