Example 1 5A: Synthesis of 3-bromo-5-methoxybenzaldehyde
3-Bromo-5-hydroxybenzaldehyde (0.5 g, 2.487 mmol) was dissolved in N,N-dimethylformamide (DMF, 14.63 mL) and the solution was cooled to 0 °C. Under stirring, sodium hydride (NaH, 0.119 g, 4.97 mmol) was added in three batches. Subsequently, the reaction mixture was slowly warmed to room temperature and iodomethane (MeI, 0.933 mL, 14.92 mmol) was added. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the reaction mixture was diluted with water and partially concentrated under reduced pressure. The concentrate was diluted with dichloromethane (DCM), washed twice sequentially with water and once with saturated brine, and then dried over anhydrous sodium sulfate (Na2SO4). After filtration to remove the desiccant, the filtrate was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography with an elution gradient of 0 to 100% ethyl acetate (EtOAc) in hexane solution to give the title compound Example 15A (0.488 g, 2.27 mmol, 9% yield).
1H NMR (400 MHz, chloroform-d) δ 9.91 (1H, s), 7.58 (1H, t, J = 1.38 Hz), 7.28-7.35 (2H, m), 3.86 (3H, s).
