The general procedure for the synthesis of 3-bromo-5-methoxybenzonitrile from the compound (CAS:867366-90-3) is as follows: a mixed solution of aldehyde 180b (12.0 g, 56 mmol), hydroxylamine hydrochloride (19.4 g, 5 eq.), ethanol (100 mL), and pyridine (10 mL) was heated to 65 °C and reacted for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and extracted by partitioning with 50% ethyl acetate/hexane and water. The organic layer was washed with brine and dried with magnesium sulfate. After evaporation of the volatiles, 12.4 g of the oxime product was obtained (97% yield). The resulting oxime was dissolved in anhydrous dioxane (100 mL) and pyridine (26 mL, 6 eq.), the solution was cooled to 0 °C and trifluoroacetic anhydride (15 mL, 2 eq.) was added slowly. Subsequently, the mixture was gradually warmed to room temperature and stirred continuously for 2 days. After that, the reaction solution was heated to 60 °C and kept for 1 hour. After completion of the reaction, the mixture was cooled to room temperature and carefully poured into ice water. The mixture was extracted with dichloromethane and the combined organic layers were washed sequentially with water, 1 M hydrochloric acid and brine. The organic layer was dried over magnesium sulfate and the solvent was evaporated to give the target product 180c 10.4 g (90% yield).
