Laboratory Study On Separation Process Of ?-thymidine Mother Liquor By Chromatography And Its Industrial Application

Beta-thymidine is an important pharmaceutical intermediate for synthesis of anti-AIDS drugs,which have a huge potential market prospect.In this paper,the separation and purification of the mother liquor of beta-thymidine is focused on.Firstly,the method of separation and purification is determined and optimized in laboratory test.Through comprehensive analysis of the literature and the experimental data,the optimum process parameters are determined.Secondly,industrialized design for separation and purification of beta-thymidine mother liquor is carried out.The equipment selection,process flow and automation design are carried out by combining the principle of three transfers and one reverse and AutoCAD modern mapping.Finally,it is successfully applied in the separation of the mother liquor with an annual processing capacity of 630 T ?-thymidine.(1)Firstly,the industrialized synthesis route of beta-thymidine is described.The target compound beta-thymidine is synthesized from 5-methyluridine by three steps: dehydration,addition and hydrogenation.Specifically,add 5-methyluridine and diphenyl carbonate to DMF,then 2,2'-dehydrated-5-methyluridine is generated with the action of catalysis by sodium bicarbonate.Then,2,2'-dehydrated-5-methyluridine reacts with HCl in ethyl acetate solvent to form 2'-chloro-2'-deoxy-5-methyluridine.Finally,2'-chloro-2'-deoxy-5-methyluridine reacts with hydrogen under Raney nickel as catalyst and sodium acetate as acid-binding agent to form beta-thymidine.Beside,2'-chloro-2'-deoxy-5-methyluridine directly entered the next reaction without purifing.So,the impurities are retained in beta-thymidine mother liquor in the crystallization process of beta-thymidine.And the impurities is produced by the side reactions of addition reaction and hydrogenation reaction.After comprehensive analysis of the content of mother liquor by liquid chromatography.We put forward a method of separation and purification of mother liquor by chromatographic column.The effects of sample volume,mobile phase,washing velocity,alcohol washing velocity and temperature to the content and yield of beta-thymidine are studied.And the optimum separation and purification process parameters are obtained.The overall yield of laboratory test is about 52.43%,and the content of beta-thymidine is about 99%.(2)On the basis of the results of laboratory test,we have further systematically completed the industrial design of separation and purification of beta-thymidine mother liquor,including material balance,energy balance,equipment selection,AutoCAD mapping and automation design.And large-scale production in the workshop is successfully realized.The annual treatment capacity of thymidine mother liquor is 600 T.Chromatographic method is used to separate and purify thymidine mother liquor.The column is filled with LSC-100 resin with the size of DN400*4000 mm.Five pieces are needed to meet the production task.In addition,the process design of reaction unit is completed by using AutoCAD modern drawing tool,and the design of automatic production is carried out scientifically.At the same time,the problems in the real process are systematically summarized and analyzed.Finally,the separation and purification of 630 T thymidine mother liquor is realized.The total yield of the workshop is 53.61%,and the content of beta-thymidine is about 99%.