Yield: 99%

Reaction Conditions:

with dihydrogen peroxide;sodium hydroxide at 80; for 1 h;

Steps:

6-Amino-2-bromo-3-methylbenzoic acid
A mixture of 3N NaOH (80 ml, 79.15 mmol) and 4-bromo-5-methyl-lH-indole-2,3-dione (19 g, 79.15 mmol) was heated at 80°C. To the solution was added hydrogen peroxide (18 ml, 176.22 mmol) slowly and the mixture was stirred for 1 hour and the mixture cooled to 5°C then acidified to pH5 with concentrated HCI. The solution was evaporated to dryness and methanol (100 ml) then added. The mixture was filtered and the filtrate was evaporated to yield 6-amino-2-bromo-3-methylbenzoic acid (18 g, 99%) as brown solid. 1H NMR (400 MHz, DMSO, 30°C) 2.21 (3H, s), 6.71 (1H, d), 7.07 (1H, d). Three exchangeable protons not observed m/z: ES+ [M+H]+ = 230.

References:

ASTRAZENECA AB;KETTLE, Jason, Grant;BAGAL, Sharanjeet, Kaur;EATHERTON, Andrew, John;FILLERY, Shaun, Michael;ROBB, Graeme, Richard;LAMONT, Scott, Gibson;KEMMITT, Paul, David;GOLDBERG, Frederick, Woolf WO2019/215203, 2019, A1 Location in patent:Page/Page column 49