Hydrochloric Acid → [2-Fluoro-4-(methylsulfanyl)phenyl]boronic acid

Participants

Reaction Steps

A stirred solution of 1-bromo-2-fluoro-4-(methylthio)benzene (180 g, 814 mmol) at −78° C. in THF (500 mL) was treated with n-BuLi (358 mL, 2.5M in hexanes, 895 mmol) over 1.5 h. After 15 min at −78° C., B(OMe)3 (254 g, 244 mol) was added over 1.5 h, and the reaction mixture was slowly warmed to ambient temperature. 10% Aqueous HCl (100 mL) was added and the mixture was stirred for 5 min. Et2O (500 mL) was added and the organic layer was separated and washed with 2M NaOH (300 mL). The aqueous phase was rinsed one more time with Et2O. The aqueous phase was then acidified with 10% aqueous HCl to pH ˜4 and the resulting solid was collected to give [2-fluoro-4-(methylthio)phenyl]boronic acid (24.7 g). 1H NMR (400 MHz, CDCl3): δ 7.70 (t, 1H, J=7.6 Hz), 7.03 (dd, 1H, Ja=8.1 Hz, Jb=1.6 Hz), 6.88 (dd, 1H, Ja=11.7 Hz, Jb=1.6 Hz), 2.49 (s, 3H).

Provenance & Evidence