Uses
3',4',5'-Trifluoroacetophenone is an organic intermediate that can be used to prepare the key mother nucleus (S)-N-[4-(1-aminoethyl)-2,6-difluorophenyl]methanesulfonamide of vanilloid compounds.
Synthesis
The general procedure for the synthesis of 3,4,5-trifluoroacetophenone from ethanoic anhydride and 3,4,5-trifluorobromobenzene was carried out as follows: firstly, iodine (361 mg, 1.42 mmol) was added to a solution of magnesium (3.53 g, 145 mmol) in tetrahydrofuran (100 ml) at room temperature, followed by slow dropwise addition of 3,4,5-trifluorobromobenzene (30.0 g, 142 mmol). The reaction mixture was stirred at the same temperature for 30 minutes. Next, a toluene solution (100 ml) containing copper (I) chloride (704 mg, 7.11 mmol) and acetic anhydride (16.0 g, 156 mmol) was added to the reaction mixture at 0°C. The reaction mixture was continued to be stirred at 0°C for 1 hour. After completion of the reaction, the mixture was poured into 2N aqueous hydrochloric acid solution and extracted with toluene. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure. The concentrated product was purified by silica gel column chromatography using ethyl acetate/hexane (1/10) as elution solvent to give 3,4,5-trifluoroacetophenone as a final yellow oil (yield 21.0 g, 85% yield).
References
[1] Patent: JP2016/84346, 2016, A. Location in patent: Paragraph 0056
[2] Patent: JP2016/84328, 2016, A. Location in patent: Paragraph 0191
