Synthesis
General procedure for the synthesis of 1-bromo-2-fluoro-4-methoxy-5-nitrobenzene from 4-bromo-3-fluoroanisole: To a solution of 1-bromo-2-fluoro-4-methoxybenzene (5.00 g, 24.39 mmol) in sulphuric acid (20.0 mL) was added potassium nitrate (2.47 g, 24.39 mmol) in batches at 0 °C. The reaction mixture was stirred continuously at 0°C for 0.5 hr. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent ratio of petroleum ether: ethyl acetate = 3:1) to confirm the completion of the reaction. The reaction mixture was quenched by slowly pouring into ice water (50.0 mL) and extracted with ethyl acetate (100 mL x 2). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to afford 1-bromo-2-fluoro-4-methoxy-5-nitrobenzene (5.55 g, 90% yield) as a white solid.
