22223-49-0

206548-14-3

General procedure for the synthesis of methyl 2-amino-5-bromo-3-methylbenzoate from methyl 2-amino-3-methylbenzoate: Methyl 2-amino-3-methylbenzoate (142.1 g, 0.843 mol, purity: 98%, quantitative NMR) was dissolved in 240 mL of water, and hydrogen bromide (48% aqueous solution, 149.2 g, 0.885 mol). Subsequently, the resulting suspension was mixed with hydrogen peroxide (30% aqueous solution, 105.1 g, 0.927 mol), and the acceleration of the drop was controlled so that the reaction was completed within 2 h and the reaction temperature was kept lower than 70°C. The reaction mixture was continued to be stirred for 1 h. After the reaction mixture had continued to be stirred for 1 h, sodium bisulphite (39% aqueous solution, 33.7 g, 0.126 mol) was added in batches until the test for peroxide was negative . The pH of the reaction mixture was adjusted to 7-8 with sodium carbonate (0.1 equiv, 9.0 g, 0.084 mol) in batches. after filtration and vacuum drying, methyl 2-amino-5-bromo-3-methylbenzoate was obtained as a light brown solid. Yield: 204.2 g, yield: 97.7%, purity: 98.5% (quantitative NMR).1H NMR (600 MHz, d6-DMSO): δ= 7.70 (d, 1H), 7.36 (pt, 1H), 6.63 (br s, 2H), 3.80 (s, 3H), 2.12 (s, 3H).