Grignard's reagent was prepared by dissolving 11.3 g of dried magnesium shavings and 75.0 g of 1-bromo-3-chloro-5-fluorobenzene (S1-1) in 220 ml of anhydrous tetrahydrofuran (THF) under nitrogen protection. The reaction system was cooled to -70 °C and 52.0 g of trimethyl borate dissolved in 200 ml of THF was slowly added dropwise. The reaction temperature of -70°C was maintained and stirred for 3 hours. Subsequently, the reaction system was gradually warmed to room temperature and stirring was continued for 12 hours. Upon completion of the reaction, 2N hydrochloric acid was slowly added dropwise to the reaction solution and stirred for 1 hour. The reaction mixture was extracted with ethyl acetate, the organic phase was washed with water and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was washed with heptane to give 34.7 g of 3-chloro-5-fluorophenylboronic acid (S1-2) in 55.7% yield.
