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Short Paper | Regular issue | Vol 104, No. 10, 2022, pp.1854-1865
Published online, 9th August, 2022
DOI: 10.3987/COM-22-14707
An Improved and Practical Synthesis of Rivaroxaban

Shovkat Olimjonov, Xiaojun Yang, Yongjian Liu, Abdullajon Odilov, Hongjian Qin, Tianwen Hu, Sharafitdin Mirzaakhmedov, Yuanchao Xie, Fuqiang Zhu,* and Jingshan Shen*

*Topharman Shanghai Co., Ltd., Building 1, No.388 Jialilue Road, Zhangjiang Hitech Park, Shanghai 201203, People’s Republic of China

Abstract

Herein we report the development of an improved and practical synthesis of rivaroxaban, an oral anticoagulant drug as a factor Xa inhibitor. The synthesis of rivaroxaban was accomplished by five steps with a total yield of 68.5% on the 220 g scale with a purity of ≥ 99% (single impurity ≤ 0.10%). The epoxy ring-opening reaction was significantly improved with the addition of the magnesium salt. Then, a plausible mechanism was proposed according to our experimental results. Three process-related impurities were identified and controlled by process optimization. The optimized synthesis is expected to offer the technical support for large scale production.