Synthesis
2,3,4-Trifluorobenzoic acid (5) (10 g, 56.8 mmol) was used as a raw material, which was dissolved in concentrated sulfuric acid (98%, 33.0 g) and stirred until completely dissolved. A mixture consisting of concentrated nitric acid (65%, 6.0 g) and concentrated sulfuric acid (98%, 6.3 g) was slowly added dropwise over a temperature range of 90 to 95 °C. The dropwise process lasted for 3.5 hours. The reaction process was monitored by thin layer chromatography (TLC, the unfolding agent was a hexane solution of 30% ethyl acetate). Upon completion of the reaction, the reaction mixture was cooled to room temperature and subsequently ice water (50 g) was added to quench the reaction. The precipitate was separated by centrifugation and dried at 50 to 55 °C for 8 hours. The crude product was purified by column chromatography and the eluent was a hexane solution of 20% ethyl acetate. Finally, the solvent was removed by distillation under reduced pressure to give the white solid product 2,3,4-trifluoro-5-nitrobenzoic acid (6) (12.2 g) in 97.1% yield.
References
[1] Journal of Chemical Research, 2015, vol. 39, # 6, p. 326 - 327
[2] Patent: WO2007/76245, 2007, A2. Location in patent: Page/Page column 18
[3] Patent: US2003/232869, 2003, A1. Location in patent: Page 9; 16
[4] Patent: WO2013/142182, 2013, A2. Location in patent: Page/Page column 21
[5] Journal of Medicinal Chemistry, 2003, vol. 46, # 10, p. 1905 - 1917
