Besides determining the kinetics of the reaction in varying temperatures, we also observed a solvent effect on reaction efficiency in line with prior reports of solvent influences on isocyanate reactivity . Common solvents previously used in reported syntheses of carmofur include pyridine, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) . In addition to this list, we included other polar aprotic solvents, which include n-methyl-2-pyrrolidone (NMP), and 2-methoxyethyl ether (diglyme) presented in Table , Entries 30-34. While we observed marginally higher yields and faster conversion in pyridine, we found that NMP was more readily removed by aqueous extraction, making it operationally more convenient. Additionally, while pyridine is a carcinogenic and has high ecotoxicity, NMP is a non-carcinogenic that has low acute toxicity via oral, dermal, and inhalation exposures, making NMP a much easier and safer solvent to handle in comparison to pyridine . There was no clear trend between solvent polarity with yield and/or conversion (Fig. ). The optimal temperature for synthesizing carmofur in pyridine is 45°C with nearly 72% NMR yield within 3 hours, which is much faster and with higher yield than previously reported literature conditions. (c) At 60°C, the reaction performed in N-methylpyrrolidinone (NMP) and pyridine had comparable endpoint yields, revealing that NMP, a safer and less toxic alternative solvent to pyridine, can be used to synthesize carmofur on-scale.