General procedure for the synthesis of 2-methoxy-4-bromobenzonitrile from methanol and 4-bromo-2-fluorobenzonitrile: 4-bromo-2-fluorobenzonitrile (15.0 g, 75.0 mmol), methanol (30.4 mL, 350 mmol), and potassium carbonate (31.1 g, 225 mmol) were dissolved in N,N-dimethylformamide (DMF, 150 mL) and the reaction was stirred overnight at 55°C under argon protection. The reaction was stirred at 55°C overnight under argon protection. Upon completion of the reaction, thin layer chromatography (TLC, spreading agent 100% dichloromethane) showed complete consumption of the material. The reaction mixture was poured into a mixture of ether (300 mL) and water (150 mL) and the organic layer was separated. The organic layer was washed sequentially with water (150 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 2-methoxy-4-bromobenzonitrile (15.2 g, 95.5% yield) as a white solid. The structure of the product was confirmed by hydrogen nuclear magnetic resonance (1H-NMR, CDCl3) and gas chromatography (GC-MS): 1H-NMR (CDCl3) δ 7.41 (d, J = 8.1 Hz, 1H), 7.16 (dd, J = 8.1, 1.6 Hz, 1H), 7.13 (d, J = 1.6 Hz, 1H), 3.93 (s, 3H); GC- MS m/z = 211 (M+), retention time (RT) = 6.15 min.
