474709-71-2

64-17-5

112704-79-7

474709-71-2

Step 1. Preparation of ethyl 4-bromo-2-fluorobenzoate To a stirred solution of 4-bromo-2-fluorobenzoic acid (1.50 g, 6.85 mmol) in dichloromethane (DCM, 26.0 mL) was added sequentially 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 1.60 g, 8.35 mmol), 4-dimethylaminopyridine (DMAP, 130 mg, 1.06 mmol) and anhydrous ethanol (EtOH, 2.00 mL). The reaction mixture was stirred at room temperature for 20 h and then washed with water and saturated saline in turn. The organic phase was dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (SiO2) with petroleum ether/ethyl acetate (1:5, v/v) as eluent to afford the target product ethyl 4-bromo-2-fluorobenzoate (1.52 g, 90% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.39 (3H, t, J = 6.8 Hz), 4.39 (2H, q, J = 6.8 Hz), 7.32-7.37 (2H, m), 7.80-7.84 (1H, m).