57381-62-1

67-56-1

936-08-3

57381-62-1

Step 1: Synthesis of methyl 2-bromo-4-chlorobenzoate. Thionyl chloride (29.2 mL, 400 mmol) was slowly added dropwise to a 500 mL two-necked round-bottomed flask containing 300 mL of anhydrous methanol at 0-5 °C (ice-water bath) for a controlled time of 10 min. After removing the ice water bath, 2-bromo-4-chlorobenzoic acid (25 g, 106 mmol) was added. The reaction mixture was heated to gentle reflux and maintained for 12 hours. The reaction progress was monitored by thin layer chromatography (TLC) and liquid chromatography-mass spectrometry (LCMS). After completion of the reaction, the reaction mixture was concentrated. The crude product was dissolved in 250 mL of dichloromethane (DCM) and washed sequentially with 50 mL of water, 50 mL of saturated aqueous sodium bicarbonate solution and 50 mL of brine. The organic phase was dried over anhydrous sodium sulfate and concentrated to afford methyl 2-bromo-4-chlorobenzoate (26 g, 99% yield), and the product was used directly in subsequent steps without further purification.