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Synthesis 2011(16): 2619-2624  
DOI: 10.1055/s-0030-1260116
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Concise Synthesis of 6-Oxa-3-azabicyclo[3.1.1]heptane Hydrotosylate

Donn G. Wishkaa, Paul Beagleyb, Jessica Lyonb, Kathleen A. Farleya, Daniel P. Walker*a
a Pfizer Worldwide Research & Development, Eastern Point Rd., Groton, CT 06340, USA
Fax: +1(860)6860013; e-Mail: daniel.p.walker.pfizer@gmail.com;
b Peakdale Molecular Ltd., Peakdale Science Park, Sheffield Rd., Chapel-en-le-Frith, High Peak, SK23 0PG, UK
Further Information

Publication History

Received 4 May 2011
Publication Date:
14 July 2011 (online)

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Abstract

Bridged bicyclic morpholines are important building blocks in medicinal chemistry research. The bicyclic morpholine 6-oxa-3-azabicyclo[3.1.1]heptane (2a) is of particular interest as a morpholine isostere because it is achiral and shows properties similar to that of morpholine based on a derived analogue. The first synthesis of morpholine 2a (tosylate salt) is described. The six-step sequence begins with inexpensive starting materials and uses straightforward chemistry.

Key words

stereoselective synthesis - bicyclic compounds - heterocycles - alkylation - hydrogenation

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19

Conditions used in the workup of the borane reduction of compound 12, see experimental section for further details.