Synthesis
The general procedure for the synthesis of 2-amino-4-bromobenzamide from 2-amino-4-bromobenzoic acid was as follows: 2-amino-4-bromobenzoic acid (10 g, 46.3 mmol) was dissolved in tetrahydrofuran (THF, 10 mL) at room temperature, 1-hydroxybenzotriazole (HOBT, 16.30 g, 106 mmol) and 1-ethyl-(3- dimethylaminopropyl)carbodiimide hydrochloride (EDC, 20.41 g, 106 mmol). Subsequently, ammonia (30 mL, 1386 mmol) was slowly added to the reaction system and the reaction was stirred at 25 °C for 30 min. The reaction was continued with stirring at the same temperature for 18 hours. Upon completion of the reaction, ethyl acetate (EtOAc, 200 mL) was added to the mixture, followed by concentration under reduced pressure to remove the solvent. The resulting organic phase was washed with saturated aqueous sodium bicarbonate (100 mL × 3) and dried with anhydrous sodium sulfate (Na2SO4). Finally, the solvent was removed by distillation under reduced pressure to afford the target product 2-amino-4-bromobenzamide (5.5 g, 24.55 mmol) in 53% yield.
References
[1] Patent: WO2012/13643, 2012, A1. Location in patent: Page/Page column 48
[2] Patent: WO2017/98440, 2017, A1. Location in patent: Page/Page column 120
[3] Patent: WO2008/23161, 2008, A1. Location in patent: Page/Page column 119
[4] Patent: WO2011/75699, 2011, A2. Location in patent: Page/Page column 206
[5] Journal of Agricultural and Food Chemistry, 2015, vol. 63, # 31, p. 6883 - 6889
