General procedure for the synthesis of 4-bromo-3,5-difluorobenzonitrile from 4-amino-3,5-difluorobenzonitrile: Sodium nitrite (3.20 g) was added to concentrated sulfuric acid (25 mL) in batches at 5 °C and the mixture was stirred for 0.5 h at room temperature. Subsequently, the mixture was cooled to 5 °C, acetic acid (40 mL) was added slowly and stirring was continued for 5 min at the same temperature. Next, 4-amino-3,5-difluorobenzonitrile (6.50 g) was added in batches and the reaction mixture was stirred at room temperature for 1 hour. The resulting mixture was transferred to a dropping funnel and slowly added dropwise over 0.5 h to a pre-prepared solution of copper (I) bromide (9.07 g) dissolved in 47 wt% hydrobromic acid (25 mL). After the dropwise addition was completed, the reaction mixture was stirred at room temperature for 13 hours. After completion of the reaction, water (300 mL) was added to the mixture and extracted with ethyl acetate. The organic layer was washed with brine and dried over a desiccant. The desiccant was removed by filtration and the filtrate was concentrated by vacuum evaporation. The resulting crude product was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to afford the white solid product 4-bromo-3,5-difluorobenzonitrile (5.00 g, 54% yield). Product characterization data: 1H NMR (DMSO-d6) δ 7.98 (2H, d, J = 6.3 Hz); EI-MS m/z 217, 219 [(M)+].
