121219-03-2

74-88-4

458-50-4

Step 1: Synthesis of 1-bromo-2-fluoro-4-methoxybenzene To a 250 mL round bottom flask was added 4-bromo-3-fluorophenol (5.0 g, 26.18 mmol, 1.00 equiv) and tetrahydrofuran (50 mL). Subsequently, potassium hydroxide (2.94 g, 52.40 mmol, 2.00 equiv) was added in batches. Under stirring, iodomethane (5.6 g, 39.45 mmol, 1.51 eq.) was added dropwise. The reaction mixture was stirred at 30°C for 4 h. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent ratio petroleum ether:ethyl acetate = 1:4). Upon completion of the reaction, the reaction was quenched by the addition of 30 mL of water. The reaction mixture was extracted with ethyl acetate (3 x 30 mL), the organic layers were combined and dried with anhydrous sodium sulfate. Subsequently, the organic layer was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography using petroleum ether as eluent to give 5.2 g (97% yield) of 1-bromo-2-fluoro-4-methoxybenzene as a yellow oil.