Synthesis
Step b: Synthesis of 4-cyano-2,6-difluorobenzoic acid
To a solution of 3,5-difluoro-4-formylbenzonitrile (0.2 g, 1.1 mmol) in dimethyl sulfoxide (10 mL) was added an aqueous solution of potassium dihydrogen phosphate (0.41 g, 2.9 mmol, dissolved in 0.4 mL of water) and sodium chlorite (0.216 g, 2.3 mmol, dissolved in 4 mL of water) in sequence. The reaction was carried out at room temperature with stirring for about 1 hour. After completion of the reaction, the reaction mixture was diluted with water (100 mL) and the aqueous phase was extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated to give 4-cyano-2,6-difluorobenzoic acid (200 mg, 91.32% yield) as a white solid.
1H NMR (400 MHz, DMSO-d6): δ 7.95 (d, J = 7.53 Hz, 2H).
References
[1] Patent: WO2012/160464, 2012, A1. Location in patent: Page/Page column 69
[2] Patent: US2014/155398, 2014, A1. Location in patent: Paragraph 0415
[3] Patent: WO2011/28685, 2011, A1. Location in patent: Page/Page column 77; 78
