The general procedure for the synthesis of 4-(hydroxymethyl)benzeneacetic acid from 4-bromomethylphenylacetic acid was as follows: 4-bromomethylphenylacetic acid (2.3 kg, 10.0 mol, 1 eq.) was added to an aqueous (90 L) solution of sodium hydroxide (1.61 kg, 40.2 mol, 4 eq.) and the resulting mixture was stirred at room temperature overnight. After confirming the complete consumption of 4-bromomethylphenylacetic acid by TLC analysis, the reaction mixture was carefully acidified with concentrated sulfuric acid (1.0 L) to a pH of about 2. Subsequently, solid sodium chloride (25 kg) was added to the mixture, followed by extraction with ethyl acetate (33 L × 3). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and concentrated until a significant amount of solid precipitated. The resulting suspension was kept at 4-6 °C overnight to promote further crystallization. The solid product was collected by filtration and the filter cake was washed with petroleum ether (2 L × 2) to afford 4-(hydroxymethyl)benzeneacetic acid (1.2 kg, yield: 71.9%). HPLC purity was 97.8% (220 nm); 1H NMR (300 MHz, DMSO-d6) δ 12.27 (s, 1H), 7.26-7.12 (m, 4H), 5.14 ( s, 1H), 4.47 (s, 2H), 3.53 (s, 2H).
