Synthesis of 14C-labeled and tritiated AMPA potentiator LY450108

Asymmetric synthesis of AMPA potentiator LY450108-[14C] containing 14C-label attached to the chiral center of the molecule, was accomplished based on Evans' chiral oxazolidinone auxiliary method. Diastereoselective methylation of p-nitrophenylacetic acid derivative was used as a key step. The auxiliary was reductively removed, and the resulting primary alcohol was converted into the corresponding amine. Its sulfonylation, reduction of the aromatic nitro group, and acylation with 3,5-difluorobenzoyl chloride led to the final product. The synthesis of tritiated LY450108 is also detailed. Copyright © 2005 John Wiley & Sons, Ltd.