Preparation method of ketorolac EP impurity D

Through the reaction of ketorolac and thionyl chloride and subsequent extraction treatment, high-purity ketorolac EP impurity D is prepared, which solves the problem of difficulty in obtaining the impurity D reference substance and achieves the quality of ketorolac tromethamine. Control and detection, and improve the yield under light-proof conditions.

CN116120325AActive Publication Date: 2023-05-16QUALITY CONTROL SOLUTIONS LTD
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Patent Information

Application Number
CN202310078986.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-01-13
Publication Date
2023-05-16
Estimated Expiration
2043-01-13

AI Technical Summary

Technical Problem

The reference standard for impurity D in ketorolac is difficult to obtain, affecting its quality control and detection.

Method used

After reacting free ketorolac with thionyl chloride, vacuum concentration, solvent extraction and column separation, combined with oxidant and alkaline treatment, 5-benzoyl-1-methoxy-2,3-di Hydrogen-1H-pyrrozine-1-carboxylic acid.

Benefits of technology

The high-purity preparation of ketorolac EP impurity D was achieved, with a purity of more than 96%, meeting the requirements for impurity reference standards, simplifying the research and detection process, and increasing the yield under light-proof conditions.

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Abstract

The invention discloses a preparation method of a ketorolac EP impurity D. The preparation method comprises the following steps: taking free ketorolac as a raw material, adding methanol for dissolving, dropwise adding thionyl chloride, and purifying to obtain 5-benzoyl-2, 3-dihydro-1H-pyrrolizine-1-carboxylic acid methyl ester; the preparation method comprises the following steps: dissolving 5-benzoyl-2, 3-dihydro-1H-pyrrolizine-1-carboxylic acid methyl ester in a solvent II, adding sodium methoxide, stirring, and adding an oxidizing agent for reaction, so as to obtain 5-benzoyl-1-methoxy-2, 3-dihydro-1H-pyrrolizine-1-carboxylic acid methyl ester; and dissolving the 5-benzoyl-1-methoxyl-2, 3-dihydro-1H-pyrrolizine-1-carboxylic acid methyl ester in a solvent III, and then adding a sodium hydroxide aqueous solution, so as to obtain the 5-benzoyl-1-methoxyl-2, 3-dihydro-1H-pyrrolizine-1-carboxylic acid. The preparation method of the ketorolac EP impurity D is simple to operate, raw materials are convenient and easy to obtain, and the ketorolac EP impurity D meets the requirement of being used as an impurity reference substance.
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