Synthesis Of Cefuroxime Sodium In One-pot Process

Cefuroxime or “Ceftin” first discovered by the Glaxo company(now Glaxo Smith Kline) in 1975 is a parenteral or oral second-generation cephalosporin antibiotics. Subsequently as a wide-spectrum antibiotic, cefuroxime plays a more and more important role on clinical use against Gram-negative bacteria and Gram-positive bacteria induced diseases. The antibacterial mechanism of Cefuroxime is that it can inhibit the cell wall synthesis of pathogenic bacteria or damage bacterial cell wall.Cefuroxime has a wide range of clinical applications, and it can be used for the treatment of postoperative infections or infections of the genitourinary system, bones,respiratory tract, joints, soft tissue and facial features and other diseases, and has a significant effect. Since 1975, Cefuroxime has been one of the international best-selling drug, is a major clinical anti-infective drugs. Cefuroxime is a second-generation cephalosporin antibiotic, is health insurance products. Domestic cefuroxime has developed rapidly in recent years, under the direct influence of cefuroxime API localization process, the rapid development of domestic preparation,cefuroxime sodium cefuroxime axetil tablets and powder production, sales grew rapidly.Now commonly used in the synthesis process is cefuroxime sodium: by 7-ACA or D-7ACA as starting materials deacylation cefuroxime acid(DCCF) intermediate deacylated cephalosporin cefuroxime cefuroxime acid intermediate acid synthesis further then through cefuroxime acid synthesis cefuroxime sodium salt. Process of deacetylation of cefuroxime acid using direct one-pot synthesis of cefuroxime sodium has not been reported.The purpose and significance of this paper: our study combines cefuroxime actual process research and development to produce, offered to D-7ACA as starting materials deacylation cefuroxime acid(DCCF) intermediates deacetylation cefuroxime acid using direct one-pot synthesis of cefuroxime sodium. Cefuroxime for optimized synthesis process were also analyzed and discussed in this work.According this work, we will further optimize the synthesis process cefuroxime sodium, improve product quality, ease of operability industrial production, as well as improve product yield, reduce product costsThe dissertation mainly includes the following aspects of content:(1) The process parameters optimization and choice of the condensation reaction.The effect of temperature on the condensation reaction were investigated, the results indicated that the purity of products is poor in the low temperature, and when the temperature rosed to 12 ?, the lacton formed by cefuroxime acid of deacylation, a by-product, increased obviously, up to 9.6%. In this paper, the effect of time on the deacylation of cefuroxime acid, the result showed that the purity of products rise in the first stage and then decrease, with the extension of reaction time of condensation.Approximately 45 min later, products of the highest purity were obtained. Thus, the appropriate temperature is-18~-22 ?, and the reaction time is 45 min based on the single factor experiment analysis.(2) The process parameters optimization and choice of the hydrolysis. The results showed when the hydrolysis temperature is 26 ?, the yield of products is the highest,however, the temperature on the purity of products has no remarkable effect. Because of incomplete hydrolysis, condensation products slightly remain in cefuroxime acid,target product, in the low temperature. So the hydrolysis temperature is 22~26 ? is more appropriate after considering all of these problems.(3) The process parameters optimization and choice of the rearrangement reaction.(4)In order to study the effect of weak base on the color of product, NH3·H2O, Na2CO3 and Na HCO3, three weak base, were used in the experiment. The results showed that the color of products is the most optimal and stable when Na HCO3 as base. The main reason is that sodium carbonate and ammonia is stranger than sodium bicarbonate,leading to product aggregation and affecting product color level. Thus, sodium bicarbonate was used in the experiment.(4) The optimization and selection of agitation speed in crystallization. On the basis of the color of products, some solvent was used to further refine to obtain the better color lever product. The results showed that the color and quality of cefuroxime Sodium is stable with the use of ethanol as solvent. More collisions of crystal can be obtained in proper agitation speed, making the solution uniform and stable, which can provide stable external environment for crystal growth. Therefore, proper agitation speed is one of the necessary conditions for crystal. The results showed the particle size distribute more centralized and uniform in the 250 r/min.(5) The analysis of solvent residue. The one pot synthesis of cefuroxime sodium,acetone and ethanol were detected in products, the main reason for residual solvent in products is that the crystal shape and drying effect of the product. Thus, the products should be dried thoroughly and solvent should be prevented to cover the products,because of coalescence crystal of products affecting the quality of products.By this topic research, the synthesis process of cefuroxime sodium will be further optimized and selected to greatly improve the quality yield of products, reduce consumption and emissions of gas and water, moreover, reducing the cost of the products, which makes industrialized production more operational.