A double ring closing metathesis reaction in the rapid, enantioselective synthesis of NK-1 receptor antagonists.
[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.
Department of Process Research, Merck Sharp & Dohme Research Laboratories, Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU, UK. debra_wallace@merck.com
D J
DJ
Wallace
J M
JM
Goodman
D J
DJ
Kennedy
A J
AJ
Davies
C J
CJ
Cowden
M S
MS
Ashwood
I F
IF
Cottrell
U H
UH
Dolling
P J
PJ
Reider
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006865:Hydrogenation; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
C426928:1-oxo-7-azaspirodecane; D001372:Aza Compounds; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds