Synthesis
General procedure for the synthesis of 3-bromo-2,6-dihydroxybenzoic acid from 2,6-dihydroxybenzoic acid: to a solution of the compound 2,6-dihydroxybenzoic acid (298 g, 1.93 mol, 1.0 eq.) and diisopropylamine (98 g, 0.97 mol, 0.5 eq.) in methylene chloride (3.5 L) was added batchwise N-bromosuccinimide (362 g, 2.03 mol, 1.05 eq.). 2.03 mol, 1.05 eq.) and the reaction was carried out at -78 °C. The reaction mixture was slowly warmed to room temperature and stirred for 16 h. The progress of the reaction was monitored by thin layer chromatography (TLC) until the reaction was completed. Upon completion of the reaction, the reaction mixture was evaporated to dryness and the residue was stirred in 1N hydrochloric acid (2L) for 0.5 hours. The precipitate was collected by filtration to afford the target compound 3-bromo-2,6-dihydroxybenzoic acid (370 g, 83% yield) as a light yellow solid.
References
[1] Patent: WO2016/149393, 2016, A1. Location in patent: Paragraph 0277
[2] Patent: WO2016/3929, 2016, A1. Location in patent: Paragraph 0336
[3] Journal of the Chemical Society, 1963, p. 497 - 506
