A double ring closing metathesis reaction in the rapid, enantioselective synthesis of NK-1 receptor antagonists

D J Wallace; J M Goodman; D J Kennedy; A J Davies; C J Cowden; M S Ashwood; I F Cottrell; U H Dolling; P J Reider

doi:10.1021/ol006958g

A double ring closing metathesis reaction in the rapid, enantioselective synthesis of NK-1 receptor antagonists

Org Lett. 2001 Mar 8;3(5):671-4. doi: 10.1021/ol006958g.

Authors

D J Wallace¹, J M Goodman, D J Kennedy, A J Davies, C J Cowden, M S Ashwood, I F Cottrell, U H Dolling, P J Reider

Affiliation

¹ Department of Process Research, Merck Sharp & Dohme Research Laboratories, Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU, UK. [email protected]

PMID: 11259033
DOI: 10.1021/ol006958g

Abstract

[structure: see text]. The NK-1 receptor antagonist 1 has been prepared in seven steps from phenylglycine methyl ester. The key steps are a double ring closing metathesis reaction of tetraene 7 to prepare spirocycle 6 and a reductive Heck reaction to introduce the aryl moiety. This latter reaction discriminates the olefins of compound 6 and proceeds in a highly regio- and stereoselective manner.

MeSH terms

Aza Compounds / chemical synthesis*
Aza Compounds / pharmacology
Hydrogenation
Neurokinin-1 Receptor Antagonists*
Spiro Compounds / chemical synthesis*
Spiro Compounds / pharmacology
Stereoisomerism

Substances

1-oxo-7-azaspirodecane
Aza Compounds
Neurokinin-1 Receptor Antagonists
Spiro Compounds