General procedure for the synthesis of 5-fluoro-2-methyl-3-nitrobenzoic acid (D135) from 2-methyl-5-fluorobenzoic acid: 2-methyl-5-fluorobenzoic acid (20 g) was added in batches to ice-cooled concentrated sulfuric acid (98%, 80 mL), and stirred until all solids were dissolved. A mixture of nitric acid (65%, 6 mL) and concentrated sulfuric acid (98%, 12 mL) was slowly added dropwise at 0°C. The solution was then mixed with a mixture of nitric acid (65%, 6 mL) and concentrated sulfuric acid (98%, 12 mL). After the dropwise addition was completed, the reaction mixture was gradually warmed to room temperature and stirring was continued for 6 hours. Upon completion of the reaction, the mixture was slowly poured into ice (500 g) to quench the reaction and precipitate a solid. The solid was collected by filtration and washed with water (100 mL). The solid was redissolved in ethyl acetate (200 mL) and the organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give the title compound (11 g) as a brown solid.1H NMR (400 MHz, MeOD-d4): δ 7.84 (dd, J = 8.7, 2.6 Hz, 1H), 7.78 (dd, J = 7.8, 2.8 Hz, 1H), 2.55 (s, 3H).MS (ESI ): m/z calculated value C8H6FNO4 [M-H]- 198, measured value 198.
