[Synthesis]
The general procedure for the synthesis of 4-chloro-3-ethoxyphenylboronic acid from 4-bromo-1-chloro-2-ethoxybenzene was as follows: n-butyllithium (n-BuLi, 1.6 M hexanes solution, 13.6 mL, 21.8 mmol) was slowly added to a solution of tetrahydrofuran (THF, 20 mL) of Intermediate 15A (3.8 g, 16 mmol) at -78 °C. The reaction mixture was stirred continuously at -78 °C for 40 min, followed by the addition of triisopropyl borate (7.43 mL, 32 mmol). The reaction system was slowly warmed from -78 °C to room temperature and stirring was continued for 18 hours. Upon completion of the reaction, the reaction was quenched with 1.0 N hydrochloric acid (50 mL) followed by extraction of the organic phase with ethyl acetate (EtOAc). The organic phase was washed with saturated saline and dried over anhydrous sodium sulfate (Na2SO4). The crude product was purified by fast column chromatography (eluent ratio of dichloromethane: ethyl acetate: methanol = 50:50:1) to give 1.85 g (57% yield) of Intermediate 15B as a white solid. Its 1H NMR (400 MHz, CDCl3) data were as follows: δ 1.53 (t, J=7.03Hz, 3H), 4.23 (d, J=7.03Hz, 2H), 7.48 (d, J=7.91Hz, 1H), 7.66 (d, J=6.15Hz, 2H). |