General procedure for the synthesis of 4-ethoxy-3-fluorophenylboronic acid from trimethyl borate and 4-bromo-2-fluorophenylethyl ether: 4-bromo-2-fluorophenylethyl ether (43.8 g) was dissolved in dry tetrahydrofuran (400 ml) and the resulting solution was cooled down to -70 °C. Under nitrogen protection, n-butyllithium (133 ml) was slowly added dropwise and the reaction was stirred at -70 °C for 2 hours. Subsequently, a dry tetrahydrofuran solution of trimethyl borate (64.8 g) was slowly added at the same temperature. The reaction solution was gradually warmed to room temperature and stirring was continued for 16 hours. Upon completion of the reaction, the reaction was quenched by the addition of 2N hydrochloric acid (200 ml) and the reaction mixture was extracted with toluene. The organic layer was washed sequentially with water and saturated aqueous sodium chloride solution and then dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give a light brown solid. Purification by recrystallization (heptane: toluene=4:1, v/v) gave colorless crystals of 4-ethoxy-3-fluorophenylboronic acid (23.9 g, yield: 65%).
