The Key Intermediates Synthesis Of Statin And Sartan

Simvastatin,one of Statin drugs and mainly used for lowering lipid level in the blood,can effectively curb the production of endogenous cholesterol,and usually used as blood-fat modifier.Losartan as important kind of sartan blood-pressure drugs,can effectively block Angiotensin II,and played a key role in regulating the blood pressure in vivo.Simvastatin and Losartan are often used to treat disease of heart head blood-vessel.With the development of Simvastatin and Losartan,the two drugs have attracted the attention of people.Therefore the process development of intermediates of Simvastatin and Losartan show great industrial value and practical significance.2,2-dimethyl butyl chloride is an important intermediate of Simvastatin.Based on he existing synthetic methods reviewed in this paper,2-methyl-2-butanol was selected as starting material and formic acid was used as carbonyl source to synthesis 2,2-dimethylbutanic acid through carbine reaction.On the other hand,the valeronitrile was chosen as the initial raw material to synthesis2-butyl-5-chloro-1H-imidazole-4-carbaldehyde,a key intermediate of Losartan,through esterification,amination,substitution,chlorofolmylation and hydrolysis reaction.The purity and structure of the intermediates and products were detected by GC,HPLC,NMR and MS.The influence factors of the yield and purity of products were investigated,including the molecular ratio of starting materials,the way of charging,the recycle times of mother liquid,reaction temperature and reaction times.Under the optimized reaction conditions,the yield of 2,2-dimethyl butyl chloride can up to 89.8% with 96.6% purity.And yield of2-butyl-5-chloro-1H-imidazole-4-carbaldehyde was 72.0% with 99.0%purity.Comparing with the related reports,the improved methods show some advantages,such as high yield,simple operation,and starting materials easy available,which make them having good future for the industial application.