Methyl 4-hydroxy-3-(trifluoromethyl)benzoate

67-56-1

220239-68-9

115933-50-1

Step 1: Synthesis of methyl 4-hydroxy-3-(trifluoromethyl)benzoate 4-Hydroxy-3-(trifluoromethyl)benzoic acid (4.9 g, 23.7 mmol) was dissolved in a solvent mixture of methanol (15 mL) and DMF (18 μL, 0.24 mmol). Thionyl chloride (5.2 mL, 71.0 mmol) was slowly added dropwise under stirring, and the dropwise addition time was controlled within 10 min. After the dropwise addition, the reaction mixture was continued to be stirred at room temperature for 18 hours. Upon completion of the reaction, the volatiles were removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and washed with saturated aqueous sodium bicarbonate (50 mL). The aqueous phase was then extracted with ethyl acetate (2 x 50 mL). All organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give methyl 4-hydroxy-3-(trifluoromethyl)benzoate (4.9 g, 93% yield) as an off-white solid. Product characterization data: 1H NMR (400 MHz, DMSO) δ 11.68 (s, 1H), 8.00-8.10 (m, 2H), 7.20-7.07 (m, 1H), 3.83 (s, 3H). ESI-MS m/z calculated: 220.0, measured: 221.0 (M + 1). Retention time: 1.41 min (3 min gradient).