New convergent one pot synthesis of amino benzyl ethers bearing a nitrogen-containing bicycle

Abstract

We report herein a new convergent one pot method for the synthesis of amino benzyl ethers containing a bicyclic amine, derived from different substituted benzyl alcohols and bicyclic amino alcohols such as tropine, pseudotropine, and 3-quinuclidinol, using chlorotrimethylsilane and sodium iodide. In order to avoid the competitive reaction with the nitrogen atom, a solution of the separately prepared alkoxide of tropine, pseudotropine, and 3-quinuclidinol was added to the preformed substituted benzyl iodides and allowed to reflux at 90 °C for 15 h under nitrogen atmosphere. This method provides an efficient alternative of the preparation of amino benzyl ethers in organic synthesis with good yields in comparison with existed methods.

GRAPHICAL ABSTRACT

KEYWORDS:

• Amino benzyl ethers
• benzyl alcohols
• bicyclic amino alcohols
• nicotinic acetylcholine receptor
• Williamson reaction

Additional information

Funding

We are grateful to the Fondo Nacional de Desarrollo Científico y Tecnológico, Chile (FONDECYT postdoctoral grant 3170061 to J.J.L. and FONDECYT grant 1130079 to E. G. P.) and FONDEQUIP grant EQM120021.