2-Fluoropyridine-4-boronic acid

Chemical Properties

Uses

Synthesis

5419-55-6

128071-98-7

401815-98-3

Step 1: 4-bromo-2-fluoropyridine (30.0 g, 0.17 mol) and triisopropyl borate (38.4 g, 0.20 mol) were dissolved in a solvent mixture of anhydrous toluene and tetrahydrofuran (THF) (4:1, 250 mL) under nitrogen protection. The reaction mixture was cooled to -78 °C, followed by slow dropwise addition of n-butyllithium (80 mL, 0.20 mol, 2.5 M hexane solution) over 30 min. After the dropwise addition was completed, stirring was continued at -78 °C for 30 min. The reaction mixture was then slowly warmed up to -20°C over 1 hr. The progress of the reaction was monitored by thin layer chromatography (TLC) (unfolding agent: petroleum ether (PE):ethyl acetate (EtOAc) = 1:1) to confirm that the raw materials were completely consumed. Upon completion of the reaction, the mixture was acidified to pH 2 with 3N HCl (50 mL) and stirred at room temperature for 15 minutes. The reaction mixture was transferred to a partition funnel and extracted with EtOAc (150 mL) and water (150 mL). The organic layer was separated, washed sequentially with water and brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give (2-fluoropyridin-4-yl)boronic acid (22.0 g, 91% yield) as a white solid.

References