Intermediate 80A: Preparation of 2-(2-methyl-5-nitrophenyl)acetic acid
A solution of 2-o-tolylacetic acid (3.54 g, 23.6 mmol) in dichloromethane (DCM, 12 mL) was slowly added to a mixture of concentrated sulfuric acid (10 mL, 188 mmol) and 90% nitric acid (1 mL, 22.4 mmol) pre-cooled to -20°C. The reaction mixture was stirred at -20 °C for 30 min, then slowly warmed to room temperature and continued to stir overnight. Upon completion of the reaction, the mixture was quenched by pouring it into ice water. The precipitated white solid was collected by filtration, washed with water and concentrated. The resulting solid was ground with ether and filtered again to give the final Intermediate 80A (2.4 g, 42% yield) as a white solid.
1H NMR (400 MHz, DMSO-d6) δ ppm: 12.62 (1H, broad peak), 8.13 (1H, d, J = 2.51 Hz), 8.04 (1H, dd, J = 8.28, 2.51 Hz), 7.47 (1H, d, J = 8.53 Hz), 3.80 (2H, s), 2.34 (3H, s).
