349-60-0

328-70-1

124-41-4

349-60-0

The general procedure for the synthesis of 3,5-bis(trifluoromethyl)anisole from 3,5-bis(trifluoromethyl)bromobenzene and sodium methanol was as follows: 25 g of 1-bromo-3,5-bis(trifluoromethyl)benzene (85 mmol) was mixed with 366 mg of copper(I) bromide (CuBr, 3 mol%), 1.57 g of 18-crown-6 (7 mol%), and 92.3 g of sodium methanol in methanol ( 30% concentration, 21% precursor concentration) were mixed and heated to 105 °C. The reaction conversion was >97% as determined by GC (total reaction time 22 h). Subsequently, the reaction mixture was poured into 175 g of water and the pH was adjusted to 5-6 by dropwise addition of hydrochloric acid and then filtered through diatomaceous earth. The aqueous phase was extracted twice with 150 g of dichloromethane. The organic phases were combined and purified by vacuum fractional distillation to afford 16.5 g of 3,5-bis(trifluoromethyl)anisole (68 mmol, 79.4% yield) with a GC purity of >98.5%.