Preparation method of 4-methylthiazolaldehyde-5

Abstract

The invention relates to a preparation method of 4-methylthiazolaldehyde-5. The method comprises the following steps of: carrying out a Vilsmeier reaction to obtain 2-thiol-4-methylthiazolaldehyde-5 (IV) by using 2-thiol-4-methylthiazol (III) as a raw material; and then in the presence of a temperature not exceeding 50 DEG C, a gage pressure of 0.06-0.2 MPa and a hydrogenation catalyst which is 0.5-7.5 times of the weight of the raw material, removing thiol groups through hydrogenation reaction to obtain the 4-methylthiazolaldehyde-5 (V) as a target product. The method has the advantages of high reaction yields in all steps, good product purity, easy obtaining of chemical raw materials, no harsh environmental protection requirement and suitability for industrial scale production. The reaction flow of the method is disclosed in the specification, wherein R in the formula is a methyl group.

Description

technical field The invention relates to a new method for preparing side chain compound 4-methylthiazolein-5 used for producing cefditoren pivoxil. Background technique Cefditoren axetil is a third-generation oral cephem drug. It is a prodrug, which is hydrolyzed into an active body after oral administration, and has a broad antibacterial spectrum and strong antibacterial activity from staphylococci to Gram-negative bacteria, and is characterized by various strains producing β-lactamase Also very stable. The drug was researched and developed by Japan's Meiji Pharmaceutical Co., Ltd., and phase I clinical research began in 1987. It was approved on April 1, 1994 and is now widely used clinically. 4-Methylthiazole aldehyde-5 is an important intermediate in the synthesis of cefditoren pivoxil, and there are many studies on its synthesis technology, but there are very few synthesis methods for industrial production. The preparation method of this compound can comprise at pres...

AI Technical Summary

Problems solved by technology

4-Methylthiazole aldehyde-5 is an important intermediate for the synthesis of cefditoren pivoxil, and there are many studies on its synthesis process, but there are very few synthetic methods for industrial production

take NH 2 As a cyclizing agent, CSH is more convenient from the perspective of cyclization, but there are positional isomer impurities, which affect the yield

And gained thiazole acid will be reduced to thiazole aldehyde then yield is low, cost is high

If the thiazole acid is made into an acid chloride and then hydrogenated (Rosenmund Reduction) to form an aldehyde compound, but the effect of the hydrogenolysis reaction is not ideal

Make the price of the product higher than the existing cost

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