A Convenient Synthesis of 1-(4-Fluorophenyl)-2-(4-pyridyl) cyclopentene from Cyclopentanone

Abstract

In the framework of investigating the role of pyridyl-substituted five-membered heterocycles as potential p38 mitogen-activated protein kinase inhibitors, we synthesized the disubstituted carbocyclic analogue, 1-(4-fluorophenyl)-2-(4-pyridyl) cyclopentene. A multistep synthesis of this compound starting from cyclopentanone is reported. Cyclopentanone was converted into 1-cy-clopentenyl-4-fluorobenzene using a Grignard reaction. The oxidation of this product with hydrogen peroxide and formic acid gave 2-(4-fluorophenyl) cyclopentanone. This ketone was activated using a neodymium salt (NdCl 3· 2LiCl) and subsequently reacted with a complexed Grignard reagent (pyMgCl· LiCl) to give the corresponding cyclopentanol derivative. Finally, dehydration of the latter alcohol led to the title compound.