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Synthesis and dehydration reaction of 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphth-2-ol: possible intermediate of Lasofoxifene

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Abstract

The paper deals with a simple and sufficient synthesis of key precursor of Lasofoxifene. The 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-3,4-dihydronaphthalene was prepared by a sequence of five reactions steps: first 1-(4-benzyloxyphenyl)-6-methoxy-3,4-dihydronaphthalene was prepared (70%), and this was quantitatively epoxidized to 7b-[4-(benzyloxy)phenyl]-5-methoxy-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene. Catalytic (ZnI2) isomerization of the epoxide gave 1-(4-benzyloxyphenyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-2-one (75%). Its subsequent reaction with phenylmagnesium bromide gave 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydro-2-naphthol (87%). Acid-catalysed dehydration of this alcohol by polyphosphoric acid (25°C) provides 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,4-dihydronaphthalene (80%). Dehydration in the system of acetic anhydride/polyphosphoric acid gives 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-3,4-dihydronaphthalene (66%).

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Acknowledgments

This work was financially supported by Zentiva PLC, the Czech Republic and by Ministry of Education, Youth and Sports of the Czech Republic (Project CI MSM 002 162 7501).

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Authors and Affiliations

  1. Zentiva PLC, Dolní Měcholupy 130, 10201, Prague, Czech Republic

    Ludmila Hejtmánková & Josef Jirman

  2. Department of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 53210, Pardubice, Czech Republic

    Miloš Sedlák

Authors
  1. Ludmila Hejtmánková
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  2. Josef Jirman
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  3. Miloš Sedlák
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Correspondence to Miloš Sedlák.

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Dedicated to Professor Vladimír Macháček on the occasion of his 65th birthday.

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Hejtmánková, L., Jirman, J. & Sedlák, M. Synthesis and dehydration reaction of 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphth-2-ol: possible intermediate of Lasofoxifene. Res Chem Intermed 35, 615–623 (2009). https://doi.org/10.1007/s11164-009-0062-4

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  • DOI: https://doi.org/10.1007/s11164-009-0062-4

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