Step 1: Synthesis of 1-bromo-3,4-difluoro-2-methoxybenzene
6-Bromo-2,3-difluorophenol (3 g, 14 mmol) was slowly added to a suspension of sodium hydride (60%, 672 mg, 16.8 mmol) in N,N-dimethylformamide (14 mL) at 0 °C. After gas release ceased, iodomethane (3.0 g, 21 mmol) was slowly added to the reaction mixture. After addition, the reaction mixture was gradually warmed to room temperature and stirred continuously for 12 hours. After completion of the reaction, the reaction was quenched with saturated sodium chloride solution. The reaction mixture was extracted with ethyl acetate (2 x 20 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: n-hexane/ethyl acetate=16/1) to afford the oily product 1-bromo-3,4-difluoro-2-methoxybenzene (2.4 g, 77% yield).
1H NMR (300 MHz, CDCl3): δ 7.26 (dt, J = 7.5, 2.4 Hz, 1H), 6.82 (dt, J = 9.2, 7.5 Hz, 1H), 4.00 (d, J = 1.5 Hz, 3H).
