Study On Synthesis Process Of 3-[(Tert-butyldimethyl Silyl) Oxy] Glutaric Anhydride

3-TBDMSO glutaric anhydride(3-[(tert-butyIdimethyl silyl)oxy]glutaric anhydride) is a synthetic statin drug side-chain of the starting material is also important pharmaceutical intermediates and organic synthesis intermediates.In this paper,the basis of previous studies,the choice of citric acid as a starting material for the fuming sulfuric acid oxidation,esterification,reduction,etheritication,saponification, dehydration and other processes of synthesis of 3-TBDMSO glutaric anhydride.Reaction of the step-by-step method for isolation of the conditions and optimized to be the optimum conditions are:n(compound 1):n(oleum)=1:1.33,the reaction time was 7h,the reaction temperature 30℃,compound 2 yield 90.0%;esterification reaction,n(2):n(ethanol)=1:5, for the esterification reaction time 4.5h,the reaction temperature is 45℃,the yield of compound 3 for 65.8%;the use of borohydride sodium reduction compounds 3,n(3):n (NaBH4)=1.25:1,the reaction temperature is 25℃,time of 5h,the yield of compound 4 for 80.0%;and 3-TBDMSC1 Etherification occurred,n(4):n(3-TBDMSC1)=1:1,imidazole as a catalyst,the reaction temperature is 30℃,reaction time 15h,the yield of compound 5 for 97.6%;saponification reaction n(5):n(NaOH)=1:3,reaction temperature is 78℃,reaction time was 4h,dehydration,and the use of acetic anhydride as dehydrating agent,n(5):n(B3 anhydride)=1:1.2,the reaction temperature is 78℃,reaction time is 1.5h,two-step reaction yield of 56.7%;product with petroleum ether after recrystallization solvent purity above 99.8, with a total yield of 26.2%.With melting point of law,IR,1HNMR products and intermediates of structure identification.In this paper,the use of NaBH4 as reducing agent instead of burning easily in the air to restore the Raney nickel compounds 3,high-yield product 4,timplified the process and improve the yield,but also an important innovation in this paper point.In this paper,in citric acid as starting material for the synthesis of five-step synthesis of 3-TBDMSO glutaric anhydride,the whole process relatively simple,relatively low cost for application prospects broad.