Hydrochloric Acid → 2-Amino-3-bromo-4-fluorobenzoic acid

Participants

Reaction Conditions

Reaction Steps

A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, addition funnel, and temperature probe. The flask was charged with 7-bromo-6-fluoroindoline-2,3-dione (719b; 11.53 g, 47.3 mmol) and 1 N NaOH (104 mL, 104 mmol) at RT; 30% hydrogen peroxide (10.62 mL, 104 mmol) was added via addition funnel over 15 min when the temperature of the brown solution raised to 45° C. The reaction mixture was stirred for 1.5 h when mostly product was observed via LCMS. The slurry was acidified to pH 7 with 2 N HCl when a solid was still present; the reaction mixture was diluted with water (100 mL) to effect stirring when it began to bubble. The slurry was then acidified to pH 1.8 with 2 N HCl (no exotherm was observed). After stirring at RT for 30 min, the slurry was filtered, washed with water, and dried in a vacuum oven to give 2-amino-3-bromo-4-fluorobenzoic acid (9.90 g, 42.3 mmol, 90% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.59 (t, J=8.61 Hz, 1H) 7.08 (br. s., 2H) 7.86 (dd, J=8.90, 6.75 Hz, 1H) 13.04 (br. s., 1H). 19F NMR (377 MHz, DMSO-d6) δ ppm −97.39 (s, 1F). MS (ESI, pos. ion) m/z: 233.9/235.9 (M+1).

Provenance & Evidence