220227-98-5

444-30-4

220227-98-5

Step 1: 2-Trifluoromethylphenol (5.0 g, 30.86 mmol) was dissolved in trifluoroacetic acid (50 mL) with hexamethylenetetetramine (8.64 g, 61.72 mmol) and the reaction was stirred at 65°C for 18 hours. After completion of the reaction, the reaction solution was concentrated and diluted with 2N aqueous hydrochloric acid. The acidic aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by fast column chromatography (Biotage FLASH 40M, silica gel column, eluent: 20% ethyl acetate/hexane) to give 2.1 g of 4-hydroxy-3-(trifluoromethyl)benzaldehyde in 36% yield. Mass spectrum (electrospray ionization) m/z: 188.9; high resolution mass spectrum (calculated value C8H5F3O2, 190.0242; measured value [ESI, M+H]+, 191.0324).