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

J Org Chem. 2009 Jul 3;74(13):4886-9. doi: 10.1021/jo900376b.

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.

MeSH terms

  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Cyclopentanes / chemical synthesis*
  • Cyclopentanes / chemistry
  • Molecular Structure
  • Receptors, Lysosphingolipid / antagonists & inhibitors*
  • Receptors, Lysosphingolipid / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Carboxylic Acids
  • Cyclopentanes
  • Receptors, Lysosphingolipid
  • methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate