Atorvastatin Calcium Synthesis Process Research

A brief review on cardiovascular and cerebrovascular diseases in the points of the actualities, pathogenesis, and developments of therapeutic medicine was given. Besides, the studies of Atorvastatin calcium, which is one of the presentatives of the new hypolipidemic drug, were smmerized in detailed including the action mechanisms, market outlook, synthetic process in detail.According to the literatures, four synthetic routes of Atorvastatin calcium were smmerized. Based on the literatures, Atorvastatin calcium can be disconnected into distinct fragments: 2-(2-(4-flurophenyl)-2-oxo-1-phenylethyl)-4-methyl-3-oxo-N-phenylpentamide(8),and(4R,6R)-tert-Butyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate.We focused on the synthetic process of compound 8 in this thesis.The compound 8 was obtained in an overall of 21.6% via seven steps in the route by using malonic acid as the starting material.This synthesis route of Atorvastatin calcium comprises nine steps in total, including some reactions, such as, chlorination, acylation,bromination, Paal-Knorr and so on. Finally, Atorvastatin calcium was synthesized successfully in an overall yield of 12.3%(from malonic acid).In this thesis,we designed a new synthetic route for intermediate 8 and study its process in detail. The structures of intermediates and the final product were identified by MS and 1H-NMR.The synthetic route is convent to operate with lower cost and high yield, and suitable for scale-up manufacture.