The general procedure for the synthesis of 5-bromo-2,3-difluorobenzonitrile using 5-amino-2,3-difluorobenzonitrile as starting material was as follows: first, copper (I) bromide (25 mg, 0.11 mmol) was dissolved in acetonitrile (1 mL) under nitrogen protection and the solution was cooled down to 0 °C. Subsequently, a solution of tert-butyl nitrite (15 mg, 0.14 mmol) and 5-amino-2,3-difluorobenzonitrile (14 mg, 0.090 mmol) in acetonitrile (1 mL) was added sequentially to this solution. The reaction mixture was stirred at room temperature for 6 hours. Upon completion of the reaction, the solvent was removed by vacuum rotary evaporation. The residue was extracted by partitioning with ethyl acetate (5 mL) and saturated aqueous sodium bicarbonate solution (5 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to give 5-bromo-2,3-difluorobenzonitrile (18 mg, 93% yield) as a yellow solid. The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.48-7.45 (m, 1H), 7.38-7.27 (m, 1H); LC/MS analysis showed m/e = 218 (M + H)+.
