Optimization Of The Synthesis Of Hypolipidemic Lipitor

By inhibiting the HMG-CoA reductase, Lipitor plays a key role for the synthesis of cholesterol and so makes the LDL particles, serum cholesterol and LDL cholesterol levels decline to effective treatment and prevention of hypercholesterolemia and mixed hyperlipidemia.This paper is a study about the optimization of synthetic route of lipitor. The key step is aminocarbonylation of tert-butyl 2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-4-iodo-5-isopropyl-3-phenyl-1H-pyrrol-1-yl)ethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate (compound 13) at atmospheric pressure by a robust acenaphthoimidazolyidene allylic palladium complex (Pd-NHC), which yield is 46.9%.At the same time, we optimized the first two steps of the route:Knoevenagel condensation reaction and Setter reaction. Through our efforts, the yields of Knoevenagel condensation reaction and Setter reaction are increased to 95.4% and 56.3%. So the yield of the two steps is increased to 53.7%.