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

Temperatur

45 °C

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).

1. additionA 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, addition funnel
2. stirringto effect stirring when it
3. customto bubble
4. stirringAfter stirring at RT for 30 min
5. filtrationthe slurry was filtered
6. washwashed with water
7. customdried in a vacuum oven

ORD-Eintrag

ord-125aebd2593b4ca1a2fd3c500f952f70

Quelldatensatz

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09394297B2