Synthesis
General procedure for the synthesis of 3-chloro-2-nitroaniline from 3-chloro-2-nitrobenzoic acid: 3-chloro-2-nitrobenzoic acid (20 g, 99 mmol) and triethylamine (Et3N, 20.74 mL, 149 mmol) were dissolved in N,N-dimethylformamide (DMF, 100 mL), followed by the addition of diphenylphosphonium chloride (32.8 g, 119 mmol). The reaction mixture was stirred at room temperature for 3 hours. Next, water (200 mL) was added to the reaction mixture and heated at 100 °C for 1 hour. After the reaction was completed, the solution was cooled to room temperature. The device was short range distillation head and DMF was removed by high vacuum distillation. the remaining solid was dissolved in ethyl acetate (EtOAc) and washed with saturated sodium bicarbonate (NaHCO3) solution. The organic phase was filtered through diatomaceous earth, the filtrate was washed sequentially with water (3 times) and brine, dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated under reduced pressure to afford the target product 3-chloro-2-nitroaniline 10 g in 53.4% yield. m/z 173.1 (M + H)+ with retention time of 1.67 min by LC-MS.
References
[1] Patent: WO2015/92713, 2015, A1. Location in patent: Page/Page column 273
[2] Journal of Organic Chemistry, 1977, vol. 42, # 1, p. 166 - 169
[3] Journal of Medicinal Chemistry, 1993, vol. 36, # 11, p. 1630 - 1640
[4] Journal of Medicinal Chemistry, 1992, vol. 35, # 23, p. 4455 - 4463
[5] Patent: US6358946, 2002, B1. Location in patent: Page column 5
