Synthesis
106.8 g (0.8 mol) of D-aspartic acid and 700 ml of methanol were added to the reaction vessel and 84.4 ml (1.2 mol) of thionyl chloride was added slowly dropwise under stirring, controlling the reaction temperature to 0°C. After the dropwise addition, the reaction system was warmed up to room temperature (about 29°C) and the reaction was continued with stirring for 30 hours. Upon completion of the reaction, excess methanol and thionyl chloride were removed from the reaction solution by distillation. The remaining oily material was dissolved in 3.5 times the volume of ether for crystallization to obtain white crystals. After filtration, the crystals were washed with ether three times and dried to finally obtain 107.8 g of white solid DL-aspartic acid dimethyl ester hydrochloride.
References
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 23, p. 10460 - 10474
[2] Journal of Organic Chemistry, 2012, vol. 77, # 5, p. 2299 - 2309
[3] Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 2936 - 2947
[4] Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226
[5] Patent: WO2010/31184, 2010, A1. Location in patent: Page/Page column 22