Separation of ursodeoxycholic acid by silylation crystallization

Abstract

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.

Keywords

Ursodeoxycholic acid / Silylation / Separation

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