Intermediate 5: Synthesis of 2-bromo-4-methoxy-1-(trifluoromethoxy)benzene; A mixture of 3-bromo-4-(trifluoromethoxy)phenol (2.0 g, 7.8 mmol), potassium carbonate (K2CO3, 1.62 g, 11.72 mmol) and iodomethane (MeI, 2.43 mL, 39.06 mmol) in acetone (13 mL) was at room temperature stirred for 10 hours. After completion of the reaction, the acetone was evaporated under reduced pressure and the crude product was diluted with dichloromethane (CH2Cl2), washed sequentially with saturated saline, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (SiO2) using a gradient elution with hexane solution of 0 to 50% ethyl acetate (EtOAc) to afford the target product Intermediate 5 (2.10 g, 99% yield).
