Precise Control of the Oxidation Reaction in a High-Purity Dexlansoprazole Synthesis Process Using In Situ Infrared

Abstract

Dexlansoprazole is a second-generation proton pump inhibitor, which is used to treat gastroesophageal reflux disease and erosive esophagitis. It is usually synthesized by asymmetric sulfur oxidation through the Kagan reaction. However, due to the difficulty in controlling the degree of sulfur oxidation, the impurity content changes in different batches in the preparation process, resulting in the low quality of obtained dexlansoprazole, which is difficult to meet the requirements of Pharmacopeia. To control the oxidation degree of sulfur and accurately judge the reaction end point, in situ infrared spectroscopy was used to monitor the reaction state in the synthesis of dexlansoprazole. This method has been successfully verified in kilogram-scale production, showing a final product yield of 72.9–73.6% with a purity of 99.86–99.89%.