2. Preparation of 1-bromo-4-chloro-2,5-difluorobenzene: Anhydrous copper(II) bromide (2.7 g, 12.1 mmol) and tert-butyl nitrite (1.56 g, 15.1 mmol) were dissolved in anhydrous acetonitrile (25 mL) under anhydrous conditions. The reaction mixture was heated to 65°C, followed by the slow dropwise addition of 4-chloro-2,5-difluoroaniline (1.65 g, 10.1 mmol) solution in anhydrous acetonitrile (2 mL), during which vigorous gas escape was observed. Upon completion of the reaction, the mixture was cooled to room temperature, poured into 2N HCl and extracted twice with ether. The organic phases were combined, washed sequentially with 2N HCl and saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by rapid chromatography on silica gel (eluent: hexane) to afford the target compound 1-bromo-4-chloro-2,5-difluorobenzene as a white solid (1.11 g, 48.4% yield).1H NMR (CDCl3) δ: 7.38 (dd, 2H), 7.21 (dd, 2H).
