General procedure for the synthesis of 2-fluoro-4-hydroxybenzoic acid from 2-fluoro-4-hydroxybenzonitrile: To a stirred solution of 2-fluoro-4-hydroxybenzonitrile (20.00 g, 145.9 mmol) in 160 mL of water was slowly added an aqueous 50% sodium hydroxide solution (40.00 g, 500.0 mmol). The reaction mixture was heated to reflux for 4 hours and subsequently cooled to room temperature. The cooled mixture was slowly poured into ice-cold concentrated hydrochloric acid and extracted with ether. The aqueous phase was adjusted to alkaline with saturated aqueous sodium bicarbonate, extracted again with ether and the ether layer was discarded. The aqueous phase was acidified with concentrated hydrochloric acid to pH < 2 and then extracted with ether. The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 2-fluoro-4-hydroxybenzoic acid as a white solid (22.90 g, 100% yield). The product was characterized by 1H NMR (300 MHz, CD3COCD3) and 19F-NMR (300 MHz, CD3COCD3) with the following data: 1H NMR δ (ppm): 9.80 (b, 1H), 7.87 (t, 1H), 6.77 (dd, 1H), 6.66 (dd, 1H); 19F-NMR δ (ppm): -108.13 (s, decoupled).
