High-Yielding Syntheses of 1-Piperidin-4-yl Butyro- and Valerolactams through a Tandem Reductive Amination−Lactamization (Reductive Lactamization)

We report a procedure for the concise and high-yielding syntheses of 1-piperidin-4-yl-substituted butyro- and valerolactams. Beginning with 1-benzyl-4-piperidone and γ- or δ-amino esters or acids, we have effected a tandem reductive amination−lactamization using sodium triacetoxyborohydride. This procedure represents an inexpensive and scaleable alternative to previous multistep syntheses of these important pharmaceutical building blocks.