Step 3. Synthesis of (5-fluorofuran-2-yl)boronic acid
Tetramethylethylenediamine (10.2 g, 87.93 mmol) was added to an anhydrous tetrahydrofuran (250 mL) solution of 5-fluorobenzofuran (10 g, 73.53 mmol). The reaction system was cooled to below -60 °C under nitrogen protection and n-butyllithium (93.75 mmol, 2.5 M hexane solution) was slowly added dropwise. After the dropwise addition, the reaction mixture was slowly warmed up to -10 °C over 45 min and stirring was continued at this temperature for 30 min. Subsequently, the reaction system was cooled again to below -60°C and triisopropyl borate (41.4 g, 220.21 mmol) was slowly added dropwise. After completion of the dropwise addition, the reaction mixture was gradually warmed to room temperature, the reaction was quenched with 2N hydrochloric acid (70 mL) and stirred for 1 hour. The pH of the aqueous layer was adjusted to 5 with sodium hydroxide solution and extracted with ethyl acetate (3 x 80 mL). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to afford the crude product (5-fluorofuran-2-yl)boronic acid (3.5 g, 26% yield), which could be used in the next reaction without further purification.
1H-NMR (300MHz, CDCl3): δ8.63 (s, 2H), 7.58-7.62 (m, 1H), 7.44-7.49 (m, 2H), 7.15-7.22 (m, 1H).
