Optimization Of The Synthesis Process Of Dihydrophenylglycine And Its Sodium Salt

Dihydrophenylglycine base and D-(-)-Dihydro phenylglycine sodium dane salt are an important kind of drug intermediates,mainly used for cephalosporin,amoxicillin and pull some of antibiotic drug intermediates.In this paper,the synthesis technology of Dihydrophenylglycine base and D-(-)-Dihydro phenylglycine sodium dane salt are studied in detail.Initially,the synthetic route of Dihydrophenylglycine base is ensured by the reaction which apply organic amine solution and phenylglycine as raw material and metallic sodium and methyl alcohol as catalyst to directly synthesize the target product.Through plenty of experiments,the optimum reaction conditions are determined that n(phenylglycine): n(sodium): n(methyl alcohol)is 1:5:9,-2 ℃ for 10 h.And the yield of the reaction could achieve 92% and the purity of the product is more than 98%.And then the synthetic route of D-(-)-Dihydro phenylglycine sodium dane salt is reestablished.After adding sodium methoxide we should remain the solution for 15 minutes,the time of that adding methyl acetoacetate is 30 minutes,after adding methyl acetoacetate reflux time is 30 minutes,time that adding dimethylbenze should be controlled in 30 minutes.n(Dihydrophenylglycine base): n(methyl acetoacetate)is 1:1.08.And the yield of the reaction could achieve 96.5% and the purity of the product is more than 98.9%.On the basis of the above experiments D-(-)-Dihydro phenylglycine sodium dane salt was synthesized by one pot method.The structure of the target product has been determined by solid proton nuclear magnetic resonance spectroscopy and infrared spectroscopy and other detection methods.And we establish the ways to comprehensively analyze the products,of which the impurities are analyzed by the method of quantitative analysis,laying the foundation for the screening of the optimum conditions.Secondly,the reuse of waste produced during the reaction is researched and the results showed that the treated material ethanediamine and dimethylbenzene can be recycled and reused,the rate of recovery is 72.2% and 91% respectively;the raw products that washed by isopropanol can be recycled nine times,verifying the thesis of this paper that the synthesis route is low cost and environmental friendly.Finally,on the basis of the laboratory test,the synthetic process of D-(-)-Dihydro phenylglycine sodium dane salt is prepared in expanding production.We complete the production task of 25 kilogram-scale,confirming that this synthetic route meets the requirements of industrial production.In conclusion,this paper identifies one-step final product producing technology that is simple and convenient,moreover the catalyst is environment friendly which can be reused with low-cost.