Aceclofenac preparation method

Abstract

The invention relates to an aceclofenac preparation method and belongs to the chemical pharmaceutical field. The method comprises a step that acidolysis of aceclofenac tert-butyl ester is carried out in a mixed solution comprising a low-molecular-weight organic acid and hydrogen halide to obtain aceclofenac. The method which allows the acidolysis of aceclofenac tert-butyl ester to be carried out in the mixed solution comprising the low-molecular-weight organic acid and hydrogen halide has the advantages of high selectivity, reduction of the fracture of the ethoxy group in aceclofenac tert-butyl ester to a lowest limit, high acidolysis reaction conversion rate, extremely-low content of diclofenac in obtained aceclofenac, easy aceclofenac refining, and high aceclofenac purity.

Description

technical field [0001] The invention relates to a preparation method of an anti-inflammatory and analgesic drug, in particular to a preparation method of aceclofenac, which belongs to the field of chemical pharmacy. Background technique [0002] Aceclofenac, chemical name is 2-((2,6-dichlorophenyl)amino)phenylacetoxyacetic acid, English name: Aceclofenac, structural formula is: [0003] [0004] This product is a newly synthesized orally effective non-steroidal anti-inflammatory analgesic (NSAIDs), which belongs to the phenylacetic acid anti-inflammatory, antipyretic and analgesic drugs. In structure, it is similar to diclofenac, aclofenac and fenclofenac In clinical practice, compared with other non-steroidal drugs (NSAIDs) in its pharmacological effects, it has a wide range of anti-inflammatory effects, strong analgesic and antipyretic effects, and gastric Toxic effect is characteristic, and the preparation method of aceclofenac reported in the literature mostly uses d...

AI Technical Summary

Problems solved by technology

Extremely difficult to remove, affecting the purity of the product

It can be seen from comprehensive existing literature that aceclofenac tert-butyl is easy to prepare and the yield is relatively high, but when the tert-butyl group is removed by acidification, it is difficult to obtain a purer product, sometimes even a mixture, vinegar Clofenac tert-butyl ester has poor specificity for removing tert-butyl group by acidification method, because aceclofenac tert-butyl ester has two alkoxy centers that can be broken, namely tert-butoxyl and ethoxyl. , in which the tert-butoxy group is easier to be broken by acid hydrolysis than the ethoxy group, and the obtained product is aceclofenac, but the ethoxy group can also be broken, and the obtained product is diclofenac

At the same time, aceclofenac can further undergo ethoxyl breakage to generate diclofenac as well. It has been proved by experiments that the acid hydrolysis reaction of aceclofenac tert-butyl ester is affected by the type of acid used, the concentration of the acid, the reaction temperature, and the acid hydrolysis reaction. Affected by factors such as time, the degree of acidolysis is difficult to control. As long as the intensity of acidolysis is large enough, under certain conditions, aceclofenac tert-butyl ester and aceclofenac will be completely acidolyzed, and the final products will all be diclofenac. Under the existing acid hydrolysis process conditions, the purity of the obtained crude product is very poor, which brings great difficulties to post-processing, especially aceclofenac and diclofenac have similar properties, and it is difficult to separate them by ordinary methods, and they often have to go through a complicated refining process. Obtain qualified product, therefore, select appropriate acidolysis agent, reasonable solvent system and reaction condition, be the key that solves the selectivity of acidolysis of aceclofenac tert-butyl ester, this is also the key that adopts aceclofenac tert-butyl ester acidolysis Decision steps for the quality and economy of the preparation of aceclofenac

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