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Synthesis 2010(20): 3433-3438  
DOI: 10.1055/s-0030-1258193
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

(Z)-5-(4-Fluorophenyl)pent-4-enoic Acid: A Precursor for Convenient and Efficient Synthesis of the Antihypercholesterolemia Agent Ezetimibe

Matej Sovaa, Janez Mravljaka, Andreja Kovača, Slavko Pečara,c, Zdenko Časarb, Stanislav Gobec*a
a Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia
b Lek Pharmaceuticals, d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia
c Institut Jo˛ef Stefan, Jamova 39, 1000 Ljubljana, Slovenia
Fax: +386(61)4258031; e-Mail: stanislav.gobec@ffa.uni-lj.si;
Further Information

Publication History

Received 25 May 2010
Publication Date:
05 August 2010 (online)

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Abstract

A convenient and efficient total synthesis of ezetimibe, an intestinal cholesterol absorption inhibitor and useful anticholesteremic agent, is described. Based on (Z)-5-(4-fluorophenyl)pent-4-enoic acid as a starting compound, and taking the synthesis through further Z-configured intermediates, the total yield is remarkably increased, compared with the use of the corresponding E-configured starting substances or intermediates.

Key words

cholesterol absorption inhibitor - (Z)-5-(4-fluorophenyl)pent-4-enoic acid - Wittig reaction - azetidinone - asymmetric synthesis

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