Synthesis Improvement Of Clindamycin Phosphata

Clindamycin phosphate is a broad-spectrum antibiotic drug,because of high efficiency,broad-spectrum,low toxicity,less side effects in clinical application is very extensive,but the process is long(ketal phosphorylation reaction to 5 step operation for 28 hours),low yield(75%),security risks and costs up to 644.3 yuan /kg.This paper adopts an improved synthesis method and condition optimization approach,using qualitative judgment and quantitative analysis of two kinds of detection methods,the development of a new production process of ketal reaction and phosphorylation synthesis of clindamycin phosphate mixed together the results of the study are as follows:(1)by improved synthesis method to clindamycin alcoholate ketal reaction after separation and purification,directly into the three and then add drops of triethylamine,acylating reagent the phosphorylation reaction.After improvement,the process is shortened from 5 steps to 2 steps,and the production cycle is shortened by 10 h.(2)were optimized by single factor test of ketal phosphorylation reaction time,temperature,three phosphorus oxychloride and three triethylamine dosage,water content in acetone is obtained for each batch,clindamycin alcoholate 110 kg,ketal phosphorus acylation reaction of the most suitable temperature for-10 to 0 degrees Celsius,the reaction time is 8h,three phosphorus oxychloride and three triethylamine dosage were 68 kg and 80 kg,acetone water content less than or equal to 0.2%,and by high performance liquid chromatography,a monitoring method of clindamycin phosphate and its intermediates,preparation of clindamycin phosphate product 88.8kg,content is 79.9%(more than 75.8% national standards for drug registration),impurity 1.8%(the standard is less than or equal to 4% national drug registration),fully meet the national standards for drug registration.Through the improvement of production process,the yield of clindamycin phosphate increased by 5%,reaching 80%,and the cost of raw materials decreased from 644.3 yuan /kg to 609 yuan /kg,and the production cycle was shortened by 10 h.The synthetic process is easy to operate,high in yield,low in cost,safe and environmentally friendly and has been put into industrialized production.