90035-20-4

402-45-9

459-57-4

90035-20-4

Intermediate 52: Synthesis of 4-{[4-(trifluoromethyl)phenyl]oxy}benzaldehyde; To a solution of 4-(trifluoromethyl)phenol (9.1 g, 56 mmol, 1.2 eq.) in N,N-dimethylformamide (DMF, 100 mL) was added sequentially cesium carbonate (22.8 g, 70 mmol, 1.5 eq.) and 4-fluorobenzaldehyde (5 mL, 46.6 mmol, 1.0 equiv). The reaction mixture was stirred and mixed at room temperature, then warmed to 85 °C and stirred continuously for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and filtered to remove the insoluble salt. The filtrate was concentrated under reduced pressure to remove the solvent, and the crude product obtained was purified by fast column chromatography (silica gel, cyclohexane/ethyl acetate=70/30, v/v) to afford the target product 4-(4'-trifluoromethyl)phenoxybenzaldehyde (9.0 g, 73% yield) as a colorless oil. The structure of the product was confirmed by 1H NMR (CDCl3, δ 9.97 (s, 1H), 7.91 (m, 2H), 7.67 (d, J=8.6 Hz, 2H), 7.20-7.11 (m, 4H)) and LCMS ((M+H)+=267, retention time Rt=3.53 min).