Example 76: In the preparation of 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7,8-dimethoxyquinoxalin-2-ylthioalkyl)ethyl]piperidin-4-yl}amide, 3,4-dimethoxy-2-nitrobenzoic acid was synthesized as follows: to a stirred 3,4-dimethoxy-2-nitrobenzaldehyde at room temperature (0.4 g, 1.9 mmol, 1.0 eq.) of acetic acid (10 mL) solution was added potassium permanganate (0.6 g, 3.8 mmol, 2.0 eq.). The reaction mixture was stirred overnight at room temperature before being quenched with saturated aqueous sodium sulfite solution and extracted with ethyl acetate (3 x 20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to give 3,4-dimethoxy-2-nitrobenzoic acid (0.35 g, 81% yield) as a white solid. The product was characterized by 1H-NMR (400 MHz, acetone-d6) and mass spectrometry (-ESI): 1H-NMR δ 7.86 (d, J=8.8 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 4.06 (s, 3H), 3.89 (s, 3H); MS m/z: 226.1 [M-H]-.
