Synthesis
The general procedure for synthesizing 3-nitro-5-(trifluoromethyl)benzoic acid from 3-trifluoromethylbenzoic acid is as follows:
1. 90% fuming nitric acid (210 mL) was slowly added to a solution of concentrated sulfuric acid (880 mL) of 3-trifluoromethylbenzoic acid (203.4 g) at 0 °C, and the addition process continued for 1 hour.
2. the reaction mixture was stirred at 35°C for 3 hours.
3. The reaction solution was slowly poured into ice (about 1 kg) to precipitate the product.
4. The precipitate was collected by filtration and washed with water (500 mL).
5. The precipitate was dissolved in ethyl acetate (500 mL) and the organic phase was washed with water.
6. After drying the organic phase, the solvent was evaporated under reduced pressure to give 3-nitro-5-(trifluoromethyl)benzoic acid (232.5 g, 92% yield) as a white powder.
1H-NMR (300MHz, CDCl3): δ 8.69 (1H, s), 8.74 (1H, s), 9.1 (1H, s).
References
[1] Patent: US2008/275085, 2008, A1. Location in patent: Page/Page column 45
[2] Journal of the American Chemical Society, 2017, vol. 139, # 43, p. 15308 - 15311
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2362 - 2380
[4] Angewandte Chemie - International Edition, 2017, vol. 56, # 8, p. 2059 - 2063
[5] Angew. Chem., 2017, vol. 129, # 8, p. 2091 - 2095,5
