Synthetic method of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid

Abstract

The invention relates to a synthetic method of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid, which belongs to the synthetic methods of heterocyclic compounds containing 1,3-thiazole ring. The synthetic method is characterized by comprising the following operation steps: 1) homogeneous oximation reaction: preparing 2-hydroxamic ethyl acetoacetate; 2) methylation reaction: preparing 2-methoxyimino ethyl acetoacetate; 3) triphosgene chlorination reaction: preparing 4-chloro-2-methoxyimino ethyl acetoacetate; 4) cyclization reaction: preparing 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid ethyl ester; 5) hydrolysis: preparing a crude product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid; and 6) refining: preparing a product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid. The invention provides an oximating agent system which is applicable to homogeneous nitrosification reaction. The invention provides a triphosgene chlorinating agent which has the advantages of small toxicity, safe and convenient storage, transportation and use, easy control of process operation and high yield. The yield of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid ethyl ester is not less than 95.4%; the yield of the crude product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid is not less than 94.4%; and the yield of the finished product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid is not less than 90.5%. The purity of the finished product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid is not less than 99.06%, and the melting point is 182.1 DEG C-183.9 DEG C. The synthetic method is used for synthesizing raw materials of the third generation of cephalosporins.

Description

technical field [0001] The invention is a method for synthesizing aminothiaxamic acid. The invention belongs to a method for synthesizing a heterocyclic compound containing a 1,3-thiazole ring, in particular to a method for preparing a heterocyclic compound with two double bonds between ring atoms without other condensed rings. Background technique [0002] The chemical name of aminothiaxamic acid is 2-(2-amino-4-thiazolyl)-2-methoxyimine acetic acid or 2-aminothiazole-4-methylhydroxamic acid, and its English name is 2-(2-Amino-4- Thiazolyl)-2-methoxyiminoacetic acid, the structural formula is: [0003] [0004] Amthioxamic acid is a raw material for the synthesis of third-generation cephalosporins. Amthioxamic acid cephalosporin antibiotics have good curative effects on infections caused by some drug-resistant bacteria and difficult-to-control pathogens, and have low toxicity and broad-spectrum long-acting effects. The curative effect is dozens of times higher than tha...

AI Technical Summary

Problems solved by technology

[0007] 1. The process of nitrosation reaction is a heterogeneous reaction, not only the slow reaction speed leads to a long period, but also the yield is low

[0008] 2. Chlorine gas is used as the chlorination agent in the chlorination process. Chlorine gas is a highly toxic gas. Once leakage occurs, it will have adverse effects on the health of operators and environmental safety, and the reaction is not easy to control

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