Study On The Synthesis Of Linezolid

Linezolid is a new antibacterial drug Pfizer Inc R & D,for the treatment of severe infections and some other antibiotics cannot treat caused by Gram positive bacteria resistant,FDA of the United States in 2000 officially permitted the drug on the market,this variety has huge market potential,the compound patent has expired.Because of the great potential of linezolid,the author of the paper decided to carry out the project.After consulting a large number of patents and documents,this paper finds that the routes reported in the literature have different degrees of defects.Finally,through the comparison,Zhang Hui,Li Guijie,Xu Hui and other reports are used for reference;Through the optimization of the process,the first step in the use of alternative butanone ethyl acetate,ethyl acetate hydrolysis may prevent recovery;use of sodium carbonate to replace three ethylamine,avoid using three triethylamine inconvenience optimized shrinkage;postprocessing method,will use the process optimization of acetone / water recrystallization for direct evaporation;to optimize the reaction temperature the reaction temperature is increased from 25 to 75 DEG C,and the reaction time from 24 hours down to 5.5h.The second step was determined using a single solvent butanone,5% palladium carbon by catalytic hydrogenation instead of ammonium formate reduction,the resulting system is more clean,the product purity is high;optimize the postprocessing method,by using direct dry way instead of dissolving,washing and drying and other complex postprocessing,greatly reduce the sewage and waste discharge.The third step experiment by optimizing the conditions,determine the experimental material ratio was determined accurately;the reaction process does not need to add water as well as the normal reaction,to avoid the difficulty of operation in water solvent recovery process;optimization of reaction temperature,the reaction temperature does not need to maintain 0-5 low temperature,so that the energy consumption the amplitude decreased;optimize the postprocessing method,to determine the product only by washing can achieve higher content,avoid the use of a large number of recrystallization solvent,thereby greatly reducing the cost;the optimal solvent can be used to determine the butanone complete the experiment,and reduces the amount of solvent,and provide necessary conditions for the repeat the use of solvents,but also for the first three steps of the continuous possible.Through the research on the continuous optimization of the synthetic conditions of the first three steps,the con-tinuous reaction before the three step,the only completed the first step reaction system of filtration,dry treatment,dry weight after weighing system,testing content,but directly to the next step,the third step until the reaction is completed,through this operation greatly reduces the labor intensity of operators,equipment use,dosage of solvent,shorten the production cycle.Finally,because the successful optimization for the first three steps of this paper,the process of the first three steps in total yield reached 92.3%,far higher than the reference in the 75.7%,the total yield was 67.7%,slightly higher than the reference in the 61.8% through the optimization of the original process,make the process cost lower.The safety of personnel is more controllable,which decreased the labor intensity greatly,sewage and waste emissions decreased greatly,small sample quality met the Pharmacopoeia requirements,reserve project resources for the future development of the company,laid the foundation for the industrial production of the company.