Method for preparing Ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate

Abstract

The invention relates to a method for preparing ethyl-demethy laminothiazolyloximate, which comprises the following steps: oximate is performed on acetylacetic ether by using nitrous acid ester in alcohol solvent, and then cyclization is performed between the solution and thiourea through bromination to prepare ethyl-demethy laminothiazolyloximate. The method mainly has the beneficial effects that both oximate and bromination intermediates need no separation and purification, and are used in the next reaction directly, so the operating steps are simplified, the route is advanced, the reaction condition is mild, the operating steps are simplified, the unit operation is avoided, the post-processing is simple, the manufacture cost is low, the yield is higher, the production of the three wastes is less, and more important implementary value and the social and economic benefits are realized.

Description

(1) Technical field

[0001] The invention relates to a preparation method of ethyl demethylaminothiaxate. (2) Background technology

[0002] Demethylaminothiaxamate ethyl ester is mainly used in the synthesis of cephalosporins, and is an important intermediate of cefotaxime, ceftriaxone, ceftazidime and other drugs.

[0003] Before the present invention was made, the synthesis of demethylthiaxamic acid ethyl ester in the prior art mainly had the following routes:

[0004] (1) With ethyl acetoacetate as raw material, there are mainly two approaches:

[0005] 1) First oximation, then halogenation, and then cyclization. Specifically: in dichloromethane, under the promotion of dilute sulfuric acid, carry out oximation reaction with sodium nitrite, the obtained ethyl 2-hydroxime acetoacetate is then halogenated with thionyl chloride or bromine, and the excess is removed under reduced pressure after the reaction Halogenating agents and organic solvents; finally, thiourea cycliza...

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