Unsaturated spirocyclic lactams stemming from a variant of the three-component Castagnoli Cushman reaction successfully underwent hydrogenation to enable access to fully saturated spirocyclic lactams. The subsequent lactam reduction gave rise to 2-spiro piperidine building blocks. The latter can be further elaborated in compound libraries and, on their own, show propensity to activate trace amineassociated receptor 1 (TAAR1), an important target for CNS disease.