Synthesis
General procedure for the synthesis of 4-chloro-3-trifluoromethoxybenzoic acid from methyl 4-chloro-3-(trifluoromethoxy)benzoate: to a methanol (30 mL) solution containing methyl 4-chloro-3-(trifluoromethoxy)benzoate (3.1 g, 12.18 mmol) was slowly added sodium hydroxide (1.46 g, 36.50 mmol) in a water ( 10mL) solution. The reaction mixture was stirred continuously for 1.5 hours at room temperature. Upon completion of the reaction, the pH of the reaction mixture was adjusted with 36% hydrochloric acid solution to 4. Subsequently, the solution was extracted with ethyl acetate (3 x 100 mL), all organic layers were combined and dried with anhydrous sodium sulfate. After filtration to remove solid impurities, the mixture was concentrated under reduced pressure to afford the target product 4-chloro-3-(trifluoromethoxy)benzoic acid as a light yellow solid (2.10 g, 74% yield). The product was analyzed by LC/MS (ES, m/z) to confirm: [M + H]+ 241.0. 1H NMR (300 MHz, DMSO) data were as follows: δ 7.92-7.99 (m, 2H), 7.40-7.47 (m, 1H).
