Industrial method for refining esomeprazole sodium salt

Abstract

The invention relates to an industrial method for refining esomeprazole sodium salt. The method is mainly characterized by comprising the following steps of: suspending the esomeprazole sodium salt in a hot poor solvent in an amount which is 1 to 10 times weight of the esomeprazole sodium salt, slowly adding a good solvent such as methanol and ethanol in an amount which is 0.5 to 1.5 times weightof the mixture, filtering while heat to obtain a clarified solution, cooling to room temperature, separating out a solid, filtering, washing and performing vacuum drying. The method is easy and convenient to implement, and inorganic impurities and organic impurities contained in the crude product of esomeprazole sodium salt, including a peroxide sulphone impurity and an R-esomeprazole impurity can be effectively removed. The esomeprazole sodium salt refined by the method has the content of over 99.5 percent, and has the single impurity content of less than 0.1 percent.

Description

technical field [0001] The invention belongs to the technical field of medicine and relates to a kind of industrialized esomeprazole sodium salt (formula ), esomeprazole sodium salt is a very effective ulcer treatment drug for the treatment of conditions such as gastric ulcer, duodenal ulcer and reflux esophagitis. [0002] [0003] Mode Background technique [0004] Omeprazole, chemical name 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfonamido]-1H-benzo Imidazole, a well-known proton pump inhibitor of gastric parietal cells, can specifically inhibit the secretion of microtubules formed by the apical membrane of parietal cells and the H + , K + -ATPase, thereby inhibiting the secretion of gastric acid. Omeprazole is a chiral compound of sulfoxide class, the sulfur atom is its stereocenter, and omeprazole is the exosome of its two monoenantiomers R-omeprazole and S-omeprazole. racemic mixture. The latter has the generic name esomeprazole. [0005] ...

AI Technical Summary

Problems solved by technology

However, its single enantiomer S-omeprazole is separated from the neutral racemate omeprazole by chiral column chromatography, and the purity requirement is very high, at least 99.0%, otherwise the amount of residual impurities cannot be guaranteed It is removed in the final step of processing esomeprazole sodium, so the preparation of starting materials using this method is cumbersome and difficult to prepare in large quantities, which is far behind industrialized production

[0014] The control of impurities in raw materials is crucial to the quality of marketed preparations. Column chromatography can effectively control the content of impurities in products, but from the perspective of industrial production, the operation is complicated and the cost is relatively high

We used the main solvent system reported in the above literature to recrystallize the crude product of esomeprazole sodium salt, but none of the desired results were obtained, and the content of esomeprazole sodium and the amount of individual impurities could not be stably controlled within the required range.