Separation of ursodeoxycholic acid by silylation crystallization

Background: Ursodeoxycholic acid is an important clinical drug in the treatment of liver disease. In our previous work, ursodeoxycholic acid was prepared by electroreduction of 7-ketolithocholic acid. The separation of ursodeoxycholic acid from the electroreduction product (47% (w/w) ursodeoxycholic acid) by silylation crystallization is described herein. Results: N,N-dimethylformamide was used as the solvent, whereas hexamethyldisilazane was the reaction agent. The optimal material ratio of electroreduction product/N,N-dimethylformamide/hexamethyldisilazane was found to be 1:10:2 (w/v/v). The reaction proceeded for 2 h at 60°C, and the corresponding silylation derivative was separated by crystallization and pure ursodeoxycholic acid was recovered by 5% acid hydrolysis at 50°C for 0.5 h. The maximum recovery and purity of ursodeoxycholic acid were 99.8% and 99.5%, respectively. Conclusion: Ursodeoxycholic acid with high purity and high recovery can be prepared directly. The developed method offers a potential application for large-scale production of ursodeoxycholic acid.