Method for preparing pantoprazole sodium sulfone-nitrogen oxidized impurity

• Main Authors: QIN CHUNXIA, ZHANG ZHAOZHEN, WU KE, LI BAOYONG, DONG TINGHUA
• Format: Patent
• Language: English
• Published: 02.12.2015
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention discloses a method for preparing a pantoprazole sodium sulfone-nitrogen oxidized impurity. The method comprises the steps: enabling 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride, which serves as a raw material, to react with 5-difluoromethoxy-2-mercapto-1H-benzimidazole so as to produce 5-difluoromethoxy-2-{[(3,4-dimethoxy-2-pyridyl)methyl]sulfo}-1H-benzimidazole; then, oxidizing 5-difluoromethoxy-2-{[(3,4-dimethoxy-2-pyridyl)methyl]sulfo}-1H-benzimidazole in the presence of hydrogen peroxide and acetic acid in a manner of using methyl rhenium trioxide as a catalyst, so as to produce a sulfone-nitrogen oxidized product of pantoprazole; and finally, forming a sodium salt by the sulfone-nitrogen oxidized product of pantoprazole and sodium hydroxide, thereby obtaining the pantoprazole sodium sulfone-nitrogen oxidized impurity. According to the method, the hydrogen peroxide-acetic acid system can oxidize a pyridine ring. The oxidizer methyl rhenium trioxide is adopted as the catalyst and can be complexed with hydrogen peroxide so as to produce peroxide of rhenium, oxygen in the peroxide of rhenium can be transferred to thioether needing oxidization, and thioether can be oxidized into sulfone through controlling the usage amount of the catalyst and the reaction temperature, so that the high-yield and high-purity product can be obtained.