Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate

Haoling Gao; Jiangang Yu; Chengsheng Ge; Qun Jiang

doi:10.3390/molecules23061440

Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate

Molecules. 2018 Jun 13;23(6):1440. doi: 10.3390/molecules23061440.

Authors

Haoling Gao^{1

2}, Jiangang Yu³, Chengsheng Ge^{4

5}, Qun Jiang⁶

Affiliations

¹ College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, China. xjguo631@sina.com.
² College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China. xjguo631@sina.com.
³ College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, China. jgyu@qzu.zj.cn.
⁴ College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, China. gechengsheng@qzu.zj.cn.
⁵ College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China. gechengsheng@qzu.zj.cn.
⁶ College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China. jiangqun1991@163.com.

Abstract

Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Brønsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail.

Keywords: asymmetric synthesis; aza-Michael/hemiacetal reaction; sitagliptin phosphate monohydrate.

MeSH terms

Catalysis
Molecular Structure
Sitagliptin Phosphate / chemical synthesis*
Sitagliptin Phosphate / chemistry
Stereoisomerism

Substances

Sitagliptin Phosphate