Generic placeholder image

Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

A New, Simple and Efficient Method for the Synthesis of 7-Azabicyclo[2.2.1]heptane Derivatives: Formal Total Synthesis of Epibatidine

Author(s): Elena Gomez-Sanchez and Jose Marco-Contelles

Volume 3, Issue 11, 2006

Page: [827 - 830] Pages: 4

DOI: 10.2174/157017806779117049

Price: $65

Abstract

The base-mediated heterocyclization of alkyl N-(c-3,t-4-dibromocyclohex-1-yl)carbamates (5, 7, 10), or N-(c-3,t-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (12) is a convenient method for the synthesis of the 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of t-butyl N-(c-3,t-4-dibromocyclohex-1- yl)carbamate (5) with sodium hydride in DMF at room temperature provided (1RS,2SR,4SR)-2-bromo-7-[(tbutoxy) carbonyl]-7-azabicyclo[2.2.1]heptane (2) in 52% yield. The t-BuOK promoted hydrogen bromide elimination of compound 2 affording 7-[(t-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (14) in 78% yield constitutes a new formal total synthesis of epibatidine (1).

Keywords: Alkyl N-(c-3,t-4-dibromocyclohex-1-yl)carbamates, N-(c-3,t-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide, 7-azabicyclo[2.2.1]heptanes, epibatidine


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy