1247885-41-1

General procedure for the synthesis of 5-amino-2,3-difluorobenzonitrile from 2,3-difluoro-5-nitrobenzonitrile: To a solution of 2,3-difluoro-5-nitrobenzonitrile (920 mg, 5.00 mmol) in acetonitrile (25 mL) was added sequentially iron powder (1.96 g, 35.10 mmol) and acetic acid (6.0 g, 99.91 mmol). The reaction mixture was stirred at room temperature for 2 h. The solids generated in the reaction were subsequently removed by filtration. The filtrate was diluted with water (100 mL) and the pH was adjusted with saturated sodium bicarbonate solution to 8. The mixture was extracted with ethyl acetate (150 mL x 2) and the organic phases were combined, washed sequentially with brine and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure and the residue was purified by neutral alumina column chromatography with the eluent ethyl acetate/hexane (0% to 65% gradient) to afford 5-amino-2,3-difluorobenzonitrile as a yellow solid (660 mg, 86% yield).

[1] Patent: US2016/376283, 2016, A1. Location in patent: Paragraph 0271; 0273
[2] Patent: WO2010/114971, 2010, A1. Location in patent: Page/Page column 237