General procedure for the synthesis of methyl 2-chloro-4-fluorobenzoate from methanol and 2-chloro-4-fluorobenzoic acid: 2-chloro-4-fluorobenzoic acid (6.5 g, 37 mmol) was dissolved in methanol (100 mL), chlorotrimethylsilane (14.0 mL, 111 mmol) was added, and the reaction was stirred for 24 hours at room temperature. Upon completion of the reaction, the solvent was removed by rotary evaporator. The residue was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, and the solvent was again removed by rotary evaporator to afford methyl 2-chloro-4-fluorobenzoate as a light yellow oil (7.01 g, 99% yield). The product was confirmed by 1H-NMR (CDCl3, 500 MHz): δ 7.93 (m, 1H), 7.22 (m, 1H), 7.06 (m, 1H), 3.95 (s, 3H) ppm; mass spectrometry (FIA) showed the molecular ion peaks m/z 189.1 (M + H); and the retention time for the HPLC analysis (Method A) was 3.37 min.
