[Synthesis]
The general procedure for the synthesis of methyl 2-bromo-4-fluoro-6-methylbenzoate from 2-bromo-4-fluoro-6-methylbenzoic acid and iodomethane was as follows: 2-bromo-4-fluoro-6-methylbenzoic acid (1.94 g, 8.33 mmol), anhydrous potassium carbonate (1.72 g, 12.5 mmol), and iodomethane (2.36 g, 17 mmol) were mixed in N,N- dimethylformamide (15 mL) at 20°C with vigorous stirring for 23 hours. After completion of the reaction, the suspension was poured into 70 mL of water for liquid-liquid separation. The product was extracted with ethyl acetate (4 × 25 mL), and the combined organic phases were washed sequentially with water (5 × 20 mL) and brine (2 × 20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to give 2.07 g (100% yield) of methyl 2-bromo-4-fluoro-6-methylbenzoate. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.18 (dd, 3JH-F = 8.1 Hz, 4JH-H = 2.4 Hz, 1H, Ar), 6.91 (dd, 3JH-F = 9.0 Hz, 4JH-H = 2.2 Hz, 1H, Ar), 3.96 (s, 3H, OCH3), 2.35 (s. 3H, CH3). |