Improvement On The Synthesis Of Cefoperazone

The development of cephalosporins was briefly desribed in this paper, and the third generation cephalosporins cefoperazone was also introduced. The technics of synthesis of cefoperazone was improved. Cefoperazone which quality accords with the standard of Chinese Pharmacopoeia was synthesized successfully.Two important intermediate compounds were studied in this paper: 4-ethyl-2,3-dioxopiperazine -1- carboxamido-p-hydroxyp- henylacetyl chloride ( OH-EPCP Chloride ) and 7-Amino-3-((l-methyl-tetrazole-5-yl)- thiomethyl)- 3 -cephem- 4 -carboxylic acid hydrochloride ( 7-TMCA ? HC1).(1) The synthesis method of OH-EPCP Chloride was designed and optimized and the traditional halogenation agents were substituted by triphosgene that is environmental friendly. The crystalline OH-EPCP Chloride was prepared for the first time; the TLC and HPLC methods for the determination of the OH-EPCP Chloride were established and the quality of product was characterized combined with ~1HNMR and IR. The new method is better than the traditionary one according to the result of comparing the product of new method with that of traditionary method.(2) During the process of preparing the other important intermediate compounds 7-TMCA ? HC1 , a new catalyzer borontrifluoride- acetonitr-ile complex ( BF3-CH3CN ) was introduced. The reaction conditions were optimized by arraning uniform test. The product's quality of new method is better than that of traditionary method.(3) Cefoperazone was prepared by OH-EPCP Chloride and 7-TMCA ? HC1 that synthesized by improved methods, and the reaction conditions were discussed.