b) Synthesis of 4-bromo-3-(hydroxymethyl)benzoic acid
A solution of lithium hydroxide monohydrate (2.278 g, 54.3 mmol) in water (12 mL) was slowly added to a solution of tetrahydrofuran (40 mL) containing methyl 3-(acetoxymethyl)-4-bromobenzoate (3.89 g), and the reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the pH was adjusted with 2 M hydrochloric acid solution to about 1. Subsequently, an appropriate amount of water and ethyl acetate were added for extraction, and the aqueous phase was re-extracted with ethyl acetate. All organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to afford the title compound 4-bromo-3-(hydroxymethyl)benzoic acid 3.06 g in 98% yield. The product was characterized by 1H NMR (500 MHz, DMSO-d6): δ 13.15 (br.s, 1H), 8.11 (d, 1H), 7.65-7.76 (m, 2H), 5.55-5.69 (m, 1H), 4.54 (d, 2H); mass spectra (ESI) m/z 229,231 [M-1]-.
