Scalable synthesis and isolation of the four stereoisomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate, useful intermediates for the synthesis of S1P1 receptor agonists.
The individual isomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate are useful intermediates for the synthesis of S1P1 receptor agonists. Herein we describe a scalable synthesis and isolation of each of the four stereoisomers of this compound in gram quantities with >98% ee and de. The utility of this approach is demonstrated by the synthesis of ((1R,3R)-1-amino-3-(4-octylphenyl)cyclopentyl)methanol in 7 steps, 11% overall yield, and >98% ee and de.
Wallace
Grier A
GA
Abbott Bioresearch Center, Medicinal Chemistry Department, 381 Plantation Street, Worcester, Massachusetts 01605, USA. grier.wallace@abbott.com
Gordon
Thomas D
TD
Hayes
Martin E
ME
Konopacki
Donald B
DB
Fix-Stenzel
Shannon R
SR
Zhang
Xiaolei
X
Grongsaard
Pintipa
P
Cusack
Kevin P
KP
Schaffter
Lisa M
LM
Henry
Rodger F
RF
Stoffel
Robert H
RH
D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D003517:Cyclopentanes; D049349:Receptors, Lysosphingolipid; C544637:methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate