Synthesis
The general procedure for the synthesis of 3-amino-5-bromobenzoic acid from 3-bromo-5-nitrobenzoic acid was as follows: concentrated hydrochloric acid (30 mL) was slowly added to a solution containing 3-bromo-5-nitrobenzoic acid (7.02 g, 28.54 mmol) and ethanol (150 mL), and the mixture was stirred for 5 min at room temperature. Subsequently, tin (II) chloride was added and the reaction mixture was stirred at 50 °C for 2 hours. After completion of the reaction, the mixture was cooled to room temperature. The pH was adjusted to 9 with 8 M sodium hydroxide solution, at which point a solid precipitated. The solids were removed by filtration. The filtrate was acidified to pH 5 with hydrochloric acid and the target product 3-amino-5-bromobenzoic acid was precipitated, which was filtered to give 5.8 g (94% yield). The product was analyzed by HPLC/MS with a retention time of 4.67 min, LRMS: m/z 216 (M-1).
References
[1] Patent: EP2196465, 2010, A1. Location in patent: Page/Page column 42; 43
[2] Patent: EP2394998, 2011, A1. Location in patent: Page/Page column 22-23
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 23, p. 10479 - 10497
[4] Justus Liebigs Annalen der Chemie, 1884, vol. 222, p. 169
[5] Organic and Biomolecular Chemistry, 2005, vol. 3, # 20, p. 3757 - 3766
