Synthesis
To a 1000 mL dry three-necked flask were sequentially added 60 g (0.416 mol) of methyl isobutyrylacetate, 120 g (1.288 mol) of aniline and 6 g of 4-dimethylaminopyridine (DMAP). Stirring was turned on and the temperature was slowly increased to an internal temperature of 100 °C and the reaction was maintained at this temperature for 16 hours. During the reaction, the methanol generated was collected by a fractionation device. At the end of the reaction, the system was cooled down to 70 °C and the unreacted aniline was recovered by distillation under reduced pressure, and a total of 74.7 g of aniline was recovered with 92% recovery. After the remaining reaction solution was concentrated to about 100 g, 1 kg of water was added, cooled to 30 °C and stirred to crystallize for more than 5 hours. The product was filtered, the cake was washed with water for 3 times, and dried to give a white solid product of 82.3 g. The product was analyzed by HPLC with a purity of 99.8% and a yield of 96.4%.
References
[1] Patent: CN106397241, 2017, A. Location in patent: Paragraph 0014; 0015; 0016; 0017; 0018; 0019; 0020; 0021
[2] Patent: WO2012/143933, 2012, A1. Location in patent: Page/Page column 21-22
[3] Organic and Biomolecular Chemistry, 2016, vol. 14, # 7, p. 2291 - 2296
[4] Synthetic Communications, 2015, vol. 45, # 24, p. 2832 - 2840
[5] Journal of Heterocyclic Chemistry, 2007, vol. 44, # 4, p. 923 - 926
