4-Amino-3,5-difluorobenzoic acid

110301-23-0

500577-99-1

The general procedure for the synthesis of 3,5-difluoro-4-aminobenzoic acid from 4-amino-3,5-difluorobenzonitrile was as follows: 4-amino-3,5-difluorobenzonitrile (354.3 mg, 2.3 mmol) was suspended in a 1 M aqueous sodium hydroxide solution (12 mL), and the resulting suspension was heated and reacted for 16 hours at 110 °C. After completion of the reaction, the mixture was cooled to room temperature and washed with ether. Subsequently, the aqueous phase was acidified to pH=2 with 10% KHSO4/Na2SO4 buffer and extracted with ethyl acetate (2×). The ethyl acetate extracts were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 3,5-difluoro-4-aminobenzoic acid (335 mg, 84% yield) as a yellow solid.1H NMR (300 MHz, chloroform-d) δ 7.66-7.58 (m, 2H).