Synthesis
General procedure for the synthesis of 2,2,2-trifluoro-1-(3-nitrophenyl)ethanone from 2,2,2-trifluoroacetophenone:
1. 20.0 g (114.9 mmol) of 2,2,2-trifluoroacetophenone was added to 80 mL of concentrated hydrochloric acid and the mixture was cooled to -10 °C.
2. a solution of 4.8 mL (114.8 mmol) of nitric acid dissolved in 20 mL of concentrated hydrochloric acid was pre-prepared at -10°C.
3. add the nitric acid solution dropwise slowly to the reaction mixture, controlling the reaction temperature to not exceed -5°C.
4. After the dropwise addition was completed, the reaction mixture was stirred at -10°C to 0°C for 1 hour.
5. Deionized water was carefully added, followed by adjusting the pH of the mixture to 9-10 with 50% aqueous sodium hydroxide solution.
6. The mixture was extracted three times with ethyl acetate, the organic phases were combined and dried over magnesium sulfate.
7. The organic phase was concentrated under pressure and the residue was purified by silica gel chromatography (mobile phase gradient: initially 2:1 cyclohexane/dichloromethane, progressively to 1:1 and finally pure dichloromethane).
8. 19.2 g of the target product was obtained in 76.2% yield.
LC-MS (Method 6): rt = 0.81 min; m/z = 236.
GC-MS (Method 1): Rt = 3.19 min; m/z = 150 (M-CF3)+.
References
[1] Patent: WO2013/100632, 2013, A1. Location in patent: Page/Page column 89; 90
[2] Patent: US2014/371219, 2014, A1. Location in patent: Paragraph 0624; 0625; 0626
[3] Patent: US2011/130445, 2011, A1. Location in patent: Page/Page column 64
[4] Patent: WO2016/131098, 2016, A1. Location in patent: Page/Page column 155
[5] Doklady Chemistry, 1985, vol. 281, p. 130 - 133
