Synthesis and dehydration reaction of 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphth-2-ol: possible intermediate of Lasofoxifene |
| |
Authors: | Ludmila Hejtmánková Josef Jirman Miloš Sedlák |
| |
Institution: | 1.Zentiva PLC,Prague,Czech Republic;2.Department of Organic Chemistry and Technology, Faculty of Chemical Technology,University of Pardubice,Pardubice,Czech Republic |
| |
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-tetrahydronaphtho1,2-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%). |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|