Step 1: Synthesis of (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid
To a tetrahydrofuran (THF, 800 mL) solution of diisopropylamine (175 mL, 1.25 mol) was added dropwise n-butyllithium (n-BuLi, 500 mL, 1.25 mol) at 0 °C. The reaction mixture was stirred at 0 °C for 40 min. Subsequently, the mixture was cooled to -78 °C. A solution of tert-butyl 4-fluoro-1H-indole-1-carboxylate (118 g, 0.50 mol) in THF (300 mL) was slowly added dropwise, followed by triisopropyl borate (231 mL, 1.00 mol). The reaction mixture was continued to be stirred at -78 °C for 40 min. The reaction process was monitored by high performance liquid chromatography (HPLC). Upon completion of the reaction, the reaction was quenched with saturated ammonium chloride (NH4Cl, 500 mL) solution. The mixture was then adjusted with 1N hydrochloric acid (HCl) to pH=6. The reaction mixture was extracted with ethyl acetate (EtOAc, 2000 mL), the organic layers were combined and washed with brine (500 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated. The resulting solid was recrystallized with ethyl acetate and petroleum ether (PE) to afford (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (93 g, 64% yield, the compound may be unstable at elevated temperatures, storage in a refrigerator is recommended).
1H-NMR (CDCl3, 400 MHz) δ: 7.77 (d, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.44 (s, 2H), 7.24 (m, 1H), 6.90 (m, 1H), 1.66 (s, 9H).
MS (M+H): 280.
