[Synthesis]
General procedure for the synthesis of 3-ethoxy-4-fluorophenylboronic acid from 2-fluoro-5-bromophenethyl ether: n-butyllithium (n-BuLi, 1.6 M hexane solution, 14.3 mL, 22.8 mmol) was slowly added to a tetrahydrofuran (THF, 60 mL) solution of 2-fluoro-5-bromophenethyl ether (3.86 g, 17.6 mmol) at -78 °C. The reaction mixture was stirred continuously at -78 °C for 40 min, followed by the addition of trimethyl borate (3.63 mL, 33 mmol). The reaction system was slowly warmed from -78 °C to room temperature and stirring was continued for 4 hours. Upon completion of the reaction, the reaction was quenched with 1.0 N hydrochloric acid (40 mL) followed by extraction of the organic phase with ethyl acetate (EtOAc). The organic layer was washed with brine and dried with anhydrous sodium sulfate (Na2SO4). After removal of solvent by evaporation under reduced pressure, the crude product was purified by grinding with ethyl acetate/hexane (1:4) solvent mixture. After filtration, the target product 3-ethoxy-4-fluorophenylboronic acid (9B, 2.2 g, 69% yield) was obtained as a white solid. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 1.42 (t, J = 7.03 Hz, 3H), 4.11 (q, J = 7.03 Hz, 2H), 7.03 (dd, J = 11.42,8.35 Hz, 1H), 7.18-7.29 (m, 2H), 7.35 (d, J = 7.91 Hz, 1H). |