Method for producing N-benzyloxy carbonyl glutamic acid

Abstract

The present invention relates to the production process of N-benzyloxy carbonyl glutamic acid, and belongs to the field of medicine chemical technology. The production process includes the reaction of glutamic acid and carbobenzoxy chloride under alkali condition to produce N-benzyloxy carbonyl sodium glutamate solution with impurity; extraction to eliminate imipurity; and processing the solution to obtain the product. The production process features that the N-benzyloxy carbonyl sodium glutamate solution with impurity is processed through pH regulation to 3-4 with acid, organic solvent extraction of impurity, pH regulation to strong acidity for separating coarse product and re-crystallization of the coarse product to obtain product. The production process is simple, low in cost, high in product quality and suitable for industrial production.

Description

technical field [0001] The invention relates to a production method of N-benzyloxycarbonyl glutamic acid. It belongs to the technical field of medicine and chemical industry. Background technique [0002] As a raw material for peptide synthesis or a pharmaceutical intermediate, N-benzyloxycarbonylglutamic acid is particularly important for large-scale production at low cost. The common synthesis process is that L-Glu reacts with benzyl chloroformate (Z-Cl) under sodium-containing alkali conditions and then reacts with diethyl ether (Et 2 O) Extraction of impurities, after acidification, the product is extracted with ethyl acetate (AcOEt) and purified (see: Huang Weide, Chen Changqing, Polypeptide Synthesis P15 Science Press, 1985). The disadvantages of this method are as follows: 1. The extraction agent is easy to decompose under alkaline conditions, which affects the extraction effect and causes the impurities to be extracted uncleanly; 2. Due to the fact that ether (Et ...

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Problems solved by technology

The disadvantages of this method are as follows: 1. The extraction agent is easy to decompose under alkaline conditions, which affects the extraction effect and causes the impurities to be extracted uncleanly; 2. Due to the fact that ether (Et 2 O) characteristics (low boiling point, flammable and explosive) lead to high requirements for large-scale production, ether (Et 2 0) the rate of recovery is low, thus the cost is high; 3. the method is designed for multiple extraction operations, so the process is loaded down with trivial details and the production cycle is long; 4. because the yield is low, it is only about 50-70%, causing the cost to be on the high side; 5. .Due to the large use of organic solvents and the low recovery rate, the production environment is difficult to guarantee and the pollution is serious