Synthesis
To a 500 mL four-necked flask equipped with a stirrer, thermometer and reflux condenser (connected to a 30% aqueous sodium hydroxide solution absorption unit), 300 g of methanol, 14.7 g (0.10 mol) of L-glutamic acid, and 30.0 g (0.25 mol) of thionyl chloride were added sequentially. The reaction mixture was heated to 60-63 °C and the reaction was stirred at this temperature for 7 hours. Upon completion of the reaction, the system was cooled to 20-25 °C, followed by the passage of nitrogen to displace the hydrogen chloride gas in the system for 30 min. Next, the excess thionyl chloride and methanol were recovered by distillation. To the residue, 100 g of methyl tert-butyl ether was added and pulped, followed by filtration to collect the solid. Upon drying, 20.8 g of L-glutamic acid dimethyl ester hydrochloride was obtained as a white solid. The product was analyzed by high performance liquid chromatography (HPLC) with 99.5% purity and 98.1% yield.
References
[1] Journal of Medicinal Chemistry, 2007, vol. 50, # 24, p. 6144 - 6153
[2] Archiv der Pharmazie, 2005, vol. 338, # 5-6, p. 281 - 290
[3] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 18, p. 6273 - 6290
[4] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 2, p. 777 - 793
[5] Patent: CN107602436, 2018, A. Location in patent: Paragraph 0053; 0054
