The general procedure for the synthesis of 5-trifluoromethylbenzoxazole from 2-nitro-4-trifluoromethylphenol and triethyl orthoformate was as follows: 2-nitro-4-(trifluoromethyl)phenol (500 mg, 2.41 mmol) and a palladium/carbon catalyst (200 mg) were added to ethanol (10 ml) at 0 °C and under argon protection. After hydrogen was passed to replace the air in the reaction system, the reaction was stirred at room temperature overnight. Upon completion of the reaction, the catalyst was removed by diatomaceous earth filtration and the filtrate was concentrated under reduced pressure. To the concentrated residue, triethyl orthoformate (2.4 ml, 14.5 mmol) was added and p-toluenesulfonic acid monohydrate (23 mg, 0.12 mmol) was added dropwise as a catalyst. The reaction mixture was heated to reflux and stirred for 3 hours under argon protection. Upon completion of the reaction, the reaction solution was concentrated to dryness. The resulting crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to give 5-trifluoromethylbenzoxazole (182 mg, 40% yield).
