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Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
Haoling Gao1,2, Jiangang Yu3, Chengsheng Ge4,5
1College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, China. xjguo631@sina.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.
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