Batch vs Continuous‐Flow Method to Synthesize N‐(3‐Acylamidopropyl)Lactams Through N−C Bond Cleavage in Amides with Amidines

Abstract The selective N−C bond cleavage of amides to create value‐added products through a transition metal‐free approach has become a significant challenge. Here, we present a method to convert amides into N ‐(3‐acylamidopropyl)lactams through sequential amide chemoselective N−C bond cleavage and amidine ring opening under mild conditions, applicable in batch and continuous flow processes. These methods utilize bench‐stable reagents and are operationally straightforward and mild, enabling synthesis on a gram scale with excellent functional group tolerance. Additionally, the synthetic feasibility of these reactions under flow conditions has proven to be highly efficient, providing N ‐(3‐acylamidopropyl)lactam derivatives with improved yields and shorter reaction time.