A. Synthesis of methyl 5-bromo-2-(trifluoromethyl)benzoate. Methyl 5-bromo-2-iodobenzoate (4.65 g, 13.64 mmol) and methyl fluorosulfonyl difluoroacetate (2.6 mL, 20.44 mmol) were dissolved in N-methyl-2-pyrrolidone (10 mL) under nitrogen protection. Copper (I) bromide (235 mg, 1.638 mmol) was subsequently added. The reaction mixture was transferred to a sealed tube and the reaction was stirred at 120 °C for 15 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate and washed with saturated aqueous sodium chloride solution. The aqueous phase was back-extracted with ethyl acetate (3 x 25 mL), the organic phases were combined and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed by concentration under reduced pressure. The residue was purified by silica gel column chromatography with hexane solution of 1-5% ethyl acetate as eluent to afford methyl 5-bromo-2-trifluoromethylbenzoate as a colorless oil (2.9 g, 10.25 mmol, 75% yield). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 8.08 (s, 1H), 8.01 (d, J = 8.20 Hz, 1H), 7.83 (d, J = 8.20 Hz, 1H), 3.90 (s, 3H).
