General procedure for the synthesis of methyl 2-fluoro-5-hydroxybenzoate from methanol and 2-fluoro-5-hydroxybenzoic acid: 2-fluoro-5-hydroxybenzoic acid (3e) (780 mg, 5 mmol) was dissolved in 100 mL of methanol. Thionyl chloride (0.8 mL, 10 mmol) was added slowly and dropwise in an ice bath (0 °C) and under stirring conditions, followed by refluxing the reaction mixture for 2 hours. After completion of the reaction, the reaction solution was concentrated and purified by column chromatography (eluent ratio of petroleum ether: ethyl acetate = 2:1) to afford methyl 2-fluoro-5-hydroxybenzoate (3f) 833 mg as a white solid in 98% yield. The product was characterized by 1H NMR (600 MHz, DMSO-d6): δ 9.73 (s, 1H), 7.20-7.18 (m, 1H), 7.13-7.09 (m, 1H), 6.99-6.97 (m, 1H), 3.80 (s, 3H); ESI-MS m/z: calculated value 170.04, measured value 171.25 [M + H]+.
