Synthesis
Freshly distilled diisopropylamine (42.5 g, 0.42 mol) was dissolved in ether under nitrogen protection and cooled to 0°C. n-Butyllithium (2.5 M, 175 mL) was slowly added and stirred continuously at 0 °C for 30 min. Subsequently, the reaction system was cooled to -60 °C and an ether solution of 2-fluoropyridine (34.0 g, 0.35 mol) was added slowly dropwise and stirring was continued at -60 °C for 1 hour. An ether solution of triisopropoxyborate (82.4 g, 0.44 mol) was added dropwise, then the mixture was gradually warmed to room temperature and stirred for 2 hours. An ether solution of pinacol (55.6 g, 0.47 mol) was added dropwise over 10 minutes, followed by glacial acetic acid (22.1 g, 0.37 mol). The reaction mixture was stirred overnight at room temperature, filtered and the filtrate was extracted with 5% aqueous sodium hydroxide solution. The pH of the aqueous phase was slowly adjusted to 6-7 with 3N hydrochloric acid, ensuring that the temperature was below 5 °C, and then extracted with ethyl acetate. The organic phases were combined and concentrated in vacuum to remove the solvent to afford the target product 2-fluoropyridine-3-boronic acid pinacol ester (27.0 g, 34% yield).
