Synthesis of 3-substituted pyrrolidin-2-ones and 3-substituted piperidin-2-ones from esters

-Lactams and -lactams present important structural moieties which are found in many pharmaceuticals, targeting a wide array of diseases. 1,2 Starting from commercially available esters, we developed a facile method for the synthesis of 3-substituted pyrrolidin-2-ones and piperidin-2-ones.To this end, the ester is -alkylated with 2-azidoethyl trifluoromethanesulfonate or 2-azidopropyl trifluoromethanesulfonate, followed by azide reduction and ring closure.A continuous flow protocol was developed for the azide -amine transformation but a batch protocol is available as well.