Step A - Synthesis of 1-bromo-4-chloro-5-fluoro-2-nitrobenzene: To a solution of 4-bromo-1-chloro-2-fluorobenzene (8.4 g, 40 mmol) and ammonium nitrate in dichloromethane (DCM, 335 mL) was slowly added trifluoroacetic anhydride (TFA anhydride, 41.3 mL) through the addition funnel over a 15-minute period, keeping the reaction temperature at 0 °C. After addition, the reaction mixture was continued to be stirred at 0 °C for 15 min, and then raised to room temperature and stirred for 2 h. The reaction was then carried out at 0 °C for 2 h. The reaction was then carried out at 0 °C for 2 h. Upon completion of the reaction, the reaction was quenched with 560 mL of saturated sodium bicarbonate (NaHCO3) solution and the organic and aqueous layers were separated. The aqueous layer was extracted with DCM and ethyl acetate (EtOAc), respectively. All organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and added to silica gel. The solvent was removed by concentration under reduced pressure and the residue was purified by fast column chromatography (elution gradient: 0 to 15% EtOAc/hexane) to afford the target product 1-bromo-4-chloro-5-fluoro-2-nitrobenzene 3.7 g in 36% yield.1H NMR (400 MHz, DMSO-d6): δ 8.46 (d, J = 6.9 Hz, 1H), 8.18 (d, J = 8.8 Hz, 1H).
