Synthesis of a potent hNK-1 receptor antagonist via an SN2 reaction of an enantiomerically pure alpha-alkoxy sulfonate.
The concise synthesis of a stereochemically rich hNK-1 receptor antagonist is described. The synthesis is highlighted by an S(N)2 reaction of an enantiomerically pure alpha-alkoxy sulfonate (orthogonally protected butane triol), which was prepared by utilizing salen-mediated hydrolytic kinetic resolution technology. A stereocontrolled acetalization was employed to connect two enantiomerically pure fragments with a high degree of diastereoselectivity.
Nelson
Todd D
TD
Department of Process Research, Merck Research Laboratories, 466 Devon Park Drive, Wayne, Pennsylvania 19087, USA. todd_nelson@merck.com
Rosen
Jonathan D
JD
Smitrovich
Jacqueline H
JH
Payack
Joseph
J
Craig
Bridgette
B
Matty
Louis
L
Huffman
Mark A
MA
McNamara
James
J
D064729:Neurokinin-1 Receptor Antagonists; D013237:Stereoisomerism; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D013451:Sulfonic Acids