Journal
JOURNAL OF ORGANIC CHEMISTRY
Volume 76, Issue 9, Pages 3113-3121Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jo1025783
Keywords
-
Categories
Funding
- UBE Industries, Ltd., Japan
Ask authors/readers for more resources
4-Fluoropyrrolidine derivatives are useful in medicinal chemistry applications such as dipeptidyl peptidase IV inhibitors. As attractive synthons for these, N-protected (2S,4S)-4-fluoropyrrolidine-2-carbonyl fluorides were synthesized in high yield by double fluorination of N-protected (2S,4R)-4-hydroxyproline with 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead). The 4-fluoropyrrolidine-2-carbonyl fluorides were converted to useful intermediates such as 4-fluoropyrrolidine-2-carboxamides, -N-methoxy-N-methylcarboxamide (Weinreb amide), -carboxylate methyl esters, and - carbonitriles in excellent yields. The crystalline N-Fmoc-cis-4-fluoropyrrolidine-2-carbonyl fluoride 2a is a particularly useful synthon due to its high yield of preparation and easy isolation as an enantiomerically pure compound by crystallization. Thus, the methodology using the synthons prepared by the stereospecific double fluorination has enabled a significant decrease in the synthetic steps needed for the preparation of the 4-fluoropyrrolidine derivatives useful for medicinal applications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available