Synthesis of a fluorinated Ezetimibe analogue

Synthesis of a fluorinated Ezetimibe analogue using radical allylation of [small alpha]-bromo-[small alpha]-fluoro-[small beta]-lactam

New J. Chem., 2015, Advance Article
DOI: 10.1039/C5NJ01969A, Paper

Atsushi Tarui, Ayumi Tanaka, Masakazu Ueo, Kazuyuki Sato, Masaaki Omote, Akira Ando

Atsushi Tarui,^a   Ayumi Tanaka,^a   Masakazu Ueo,^a  Kazuyuki Sato,^a   Masaaki Omote^a and   Akira Ando*^a  

 

*Corresponding authors

^aFaculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Japan
E-mail: aando@pharm.setsunan.ac.jp

A facile and efficient synthesis of a fluorinated Ezetimibe analogue was achieved by radical allylation, Wacker oxidation, and nucleophilic arylation of [small alpha]-bromo-[small alpha]-fluoro-[small beta]-lactam

The synthesis of an α-fluoro-β-lactam-containing Ezetimibe analogue was accomplished starting from α-bromo-α-fluoro-β-lactam which was readily prepared from ethyl dibromofluoroacetate. A facile and efficient method for the introduction of the C3 alkyl side chain was realized via radical allylation. The diastereoselective allylation of α-bromo-α-fluoro-β-lactam was successfully applied to construct the relative configuration of the β-lactam nucleus between C3 and C4. Further modification of the allyl side chain gave the 3′-(4-fluorophenyl)-3′-hydroxypropyl group through Wacker oxidation and nucleophilic arylation.
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