Synthesis And Characterization Of Key Intermediate Atorvastatin Calcium ATO-10 And Its Main Impurities

Atorvastatin is a new generation of HMG-CoA reductase inhibitors (blood lipid lowering agent of statins class). Not only cholesterol but also triglyceride (TG) can be lowered and it is more effective than other statins such as simvastatin, pravastatin, fluvastatin and lovastatin.With a daily oral dose of 10 mg/d LDL-C can be decreased by 40%; with a 20-40mg/d daily dose by 30% of TG, and the event of coronary heart disease and its mortality can also be decreased.This paper used ATO-8 as a main raw material, then via hydrogenation with catalyst to get ATO-9, after that condensation with M4 to obtain the desired compound (ATO-10).We improved the synthetic process of ATO-9 and ATO-10.Experiment results showed that optimum experimental condition of ATO-9 was: n(ATO-8):n(NH3):n(Ni):n(catalyst)=1:10:4:0.02, reacted at 40℃ for 6h under 0.2Mpa pressure.Meanwhile the optimal process of ATO-10 was that n(ATO-9):n(M4): n(pivalic acid)=l:0.9:0.3,reacted for 40h under refluxing.At the same time, we studied the quality of ATO-10 and prepared six impurities, finally the key intermediate (ATO-10) has been confirmed by element analysis, IR, NMR and MS.