Cephalosporin Synthesis Of Cefoxitin Sodium

Cefoxitin, the second-generation cephalosporins is permanence andhave a broad spectrum of antibacterial activity. There is no paper on thetotal synthesis of it in China. In this paper, Stanting from cefalotin sodium,the cefoxitin was obtained via 3 steps including methoxylation,deacetylation, and carbamoylation. We have improved the originalprocess.First, orthogonal design expeiriment and single factor experiment wasemployed to optimum the process. Orthogonal design expeirimentsuggested that the order of influence is reaction temperature,ratio ofcefalotin to methoxyl sodium,reaction time,ratio of Cefalotin to NBS. Theoptimum condition that reaction temperature is -60℃,ratio of Cefalotin:NBS) is 1:1.5,ratio of cefolotin:methoxyl sodium is 1:25,reaction time is 6hours. The IR spectrum and high perform liquid chromatoaphy is used tocomfirm the product. The yield is 89.8％and the purity is 97.6％.Then, single factor experiment was employed to optimum the reactionof intermediateⅥto intermediateⅤ, the reaction factor. The optimumcondition is that reaction temperature is-25℃, pH is 10, and reaction timeis 10. The product is detected by high perform liquid chromatography.The purity is 98.6％and the yield is 65.6％Finally, we employed orthogonal design expeiriment and single factorexperiment to optimum the process. Orthogonal design expeirimentsuggested that the order of influence is feeding speed, reaction time,ragent ratio. The optimum condition is feeding speed is 12d/min,reactiontemperature is -55℃, reagent ratio is 1:1.5,reaction time is 12 hours. TheIR spectrum and high perform liquid chromatoaphy is used to comfirmthe product. The yield is stable in 64.9％and the purity is 99.5％.