Based on these results, we next assessed the scope of the difluoromethylation of biologically active lactams under optimal conditions at room temperature (Figure ). First, the commercially available Sildenafil Lactam, used to treat erectile dysfunction, was applied for difluoromethylation. However, surprisingly O-difluoromethylated product is obtained in 72% isolated yield (11a). Similarly, Triacetyl-ganciclovir, an orally active antiviral agent, also delivered an O-difluoromethylated product with a 61% yield (11b). Also, the Brexpiprazole intermediate (an antipsychotic drug) and a simple pyridinone system gave O-difluoromethylated products in 73% and 91% yield, respectively (11c and 11d). It is well known that in the presence of a polar aprotic solvent, either at room temperature or higher temperature, the lactam form becomes a more stable form from its tautomeric lactim form owing to its extra stabilization through resonance. Gratifyingly, our reaction conditions (DMF as a polar aprotic solvent at room temperature) are completely in favor of lactam form, in which nucleophilicity and localization of lone pair of electrons on the O-atom are higher as compared to the N-atom. We believe this could be a probable reason for selective O-difluoromethylation instead of N-difluoromethylation with lactams. All these products (11a-11d) are isolated for the first time to furnish novel medicinally relevant O-CF2H motifs. Overall, this approach provides a simple and straightforward route for drug discovery applications. Scaling up the production of fluorinated compounds poses a significant challenge in medicinal chemistry because of the costs associated with fluorinating reagents, specialized equipment, safety standards, and maintaining precise reaction conditions. By keeping this in mind and to demonstrate the synthetic utility of our simplified protocol, we conducted the difluoromethylation with N-(3-fluoro-4-morpholinophenyl)quinolin-4-amine (1a) on the 142-mmol scale (>50 gram) and achieved the desired product (E)-1-(difluoromethyl)-N-(3fluoro-4-morpholinophenyl)quinolin-4(1H)-imine (3a) in 89% isolated yield (for experimental set-up and reaction procedure, see ESI, Figure ), and the performance of this scale-up is virtually identical with 0.5 mmol-scale of the reaction, displaying the easiness of the method (Figure ).