Study On Synthetic Process Of Cefditoren Pivoxil

Cefditoren pivoxil is one of important β-lactam types of cephalosporin drugs,usually be used in the treatment of pneumonia,urinary tract infection,septicaemia,meningitis and other serious infections.A large number of organic solvents and strong corrosion catalysts were used in the traditional method of synthesis of cefditoren pivoxil,which may damage the environment.And green synthesis technology not only can reduce or even avoid the use of organic solvents,also can improve product yield on the basis of which in a traditional method,so as to solve the environmental pollution problems caused by the synthesis of cefditoren pivoxil in the traditional method.In this paper,green synthesis technology will be(mainly including solvent-free method and the water phase method)applied to the synthesis of cefditoren pivoxil in three steps,mainly including Wittig reaction,amidation reaction and esterification reaction.The specific work carry out in this thesis is summarized as follows:(1)Taking 7-ACA,triphenylphosphine and 4-methyl-5-formyl thiazole as raw material,synthesize the 7-ATCA in LiCl solution,and different kinds and dosages of catalyst,reaction temperature,reaction time and reactant molar ratio on the reaction were discussed.The result is that in the optimum conditions [LiOH catalyst for 15 mol%,the reaction temperature was50 ℃,the reaction time was 1.5 hours and mole ratio of reactants(7-ACA: triphenylphosphine: 4-methyl-5-formyl thiazole)was 1:1.8:1.2],the yield of 7-ATCA can reach to 84 %.(2)Taking 7-ATCA and AE-active ester as raw material,under the catalyst of solid sodium hydroxide,synthesize the cefditoren in a solid state grinding process.And different kinds and dosages of catalyst,milling time,post-processing time and temperature on the reaction were discussed.The result is that in the optimum conditions [NaOH catalyst for 10 mol%,the milling time was 50 min,the post-processing temperature was 60℃,the post-processing time was 20 min and the mole ratio of reactants(7-ATCA: AE active ester)was 1:1.4],the yield of cefditoren can reach to 87%.(3)Taking cefditoren and iodomethyl pivalate as raw material,under the catalyst of immobilized lipase Lipozyme 435,synthesize the cefditoren pivoxil in solvent-free method,and different kinds and dosages of catalyst,reaction time,reaction temperature and reactant molar ratio on the reaction were discussed.The result is that in the optimum conditions [Lipozyme 435 catalyst for 6 w%,the reaction temperature was 80 ℃,reaction time was 1 hous,the mole ratio of reactants(cefditoren: iodomethyl pivalate)was 1:1.4],the yield of cefditoren pivoxil can reach to 85%.