The general procedure for the synthesis of (S)-5-benzyl 1-tert-butyl 2-aminoglutarate hydrochloride from tert-butyl acetate and L-glutamic acid 5-benzyl ester was as follows: L-glutamic acid 5-benzyl ester (75 g) was dissolved in 750 ml of tert-butyl acetate, and the temperature of the reaction system was maintained at a temperature of less than 5°C by cooling the system with ice water from an external source. 26 ml of perchloric acid was added dropwise slowly in this condition, and after completion of addition, the temperature of the reaction system was raised to 25°C. The reaction was monitored by TLC until complete conversion of L-glutamic acid 5-benzyl ester. After completion of the addition, the temperature of the reaction system was raised to 25°C and the reaction was monitored by TLC until complete conversion of L-glutamic acid 5-benzyl ester. After the reaction was completed, the pH of the reaction solution was adjusted to 7-8 with aqueous sodium carbonate, and the aqueous and organic layers were separated. The organic layer was washed sequentially with water and brine and subsequently dried with anhydrous sodium sulfate. After filtration to remove the desiccant, tert-butyl acetate was removed by vacuum distillation at 50°C to obtain an oil. The oily substance was diluted with a small amount of ether and the pH was subsequently adjusted to 4-5 by addition of a pre-prepared ether hydrochloride solution, at which time the product precipitated. The precipitate was collected by filtration and dried to give 90 g of (S)-5-benzyl 1-tert-butyl 2-aminopentanedioate hydrochloride with a purity of 98.5% and a final yield of 80%.
