Synthesis
To a 500 mL four-necked round-bottomed flask equipped with a mechanical stirrer, a thermometer and a reflux condenser tube (connected to a 30% aqueous sodium hydroxide solution absorption system), 300 g of ethanol, 14.7 g (0.10 mol) of L-glutamic acid, and 25.0 g (0.08 mol) of triphosgene were added sequentially. The reaction mixture was heated to 70-75°C and maintained at this temperature with stirring for 5 hours. Upon completion of the reaction, the system was cooled to 20-25°C and the hydrogen chloride gas generated in the system was removed by nitrogen displacement, a process that lasted for 30 minutes. Subsequently, the excess triphosgene and ethanol were recovered by distillation. To the residue, 100 mL of methyl tert-butyl ether was added for pulping, and after filtration and drying, 23.5 g of the white solid product L-glutamic acid diethyl ester hydrochloride was obtained. The product was analyzed by liquid chromatography with 99.7% purity and 98.0% yield.
References
[1] Synthetic Communications, 2010, vol. 40, # 8, p. 1161 - 1179
[2] Patent: CN107602436, 2018, A. Location in patent: Paragraph 0051; 0052
[3] Patent: CN108218739, 2018, A. Location in patent: Paragraph 0116; 0117
[4] Chemistry of Natural Compounds, 1994, vol. 30, # 2, p. 238 - 244
[5] Khimiya Prirodnykh Soedinenii, 1994, # 2, p. 261 - 268
