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Synfacts 2007(2): 0129-0129  
DOI: 10.1055/s-2006-955763
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of an NK-1 Receptor Antagonist

Contributor(s): Philip Kocienski
J. T. Kuethe*, J.-F. Marcoux, A. Wong, J. Wu, M. C. Hillier, P. G. Dormer, I. W. Davies, D. L. Hughes
Merck & Company, Rahway, USA
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Publication History

Publication Date:
23 January 2007 (online)

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Significance

Neurokinin-1 (NK-1) is implicated in numerous disorders such as anxiety, asthma, emesis, cystitis migraine, pain and psoriasis. A major challenge in the synthesis of the NK-1 receptor antagonist depicted above was the stereoselective construction of the ether link between two hindered secondary alkyl centers. A detailed mechanistic study established conditions for the etherification through an unprecedented SN2 mechanism under typical SN1 conditions.