title: 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.
abstract: 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.
authors.affiliation: Abbott Bioresearch Center, Medicinal Chemistry Department, 381 Plantation Street, Worcester, Massachusetts 01605, USA. grier.wallace@abbott.com
authors.forename: Grier A
authors.initials: GA
authors.lastname: Wallace
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Gordon
authors.forename: Martin E
authors.initials: ME
authors.lastname: Hayes
authors.forename: Donald B
authors.initials: DB
authors.lastname: Konopacki
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Fix-Stenzel
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Pintipa
authors.initials: P
authors.lastname: Grongsaard
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Cusack
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schaffter
authors.forename: Rodger F
authors.initials: RF
authors.lastname: Henry
authors.forename: Robert H
authors.initials: RH
authors.lastname: Stoffel
mesh_terms: 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
chemical_list: D002264:Carboxylic Acids; D003517:Cyclopentanes; D049349:Receptors, Lysosphingolipid; C544637:methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate