Study On Calcium Synthesis Technology Of Pitavastatin

Objective:Pitavastatin is recently approved statin, and regarded as super one, due to its strong inhibition of HMG-CoA reductase, liver-selective action, excellent pharmacokinetic properties and good security. It is vitally important to study the synthetic method suitable for industry.Methods:The side chain was synthesized from t-Butyl(3R,5S)-6-acetoxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate by hydrolysis reaction and Swern oxidation successively.Pitavastatin calcium was prepared from 3-Cyclopropyl-3-oxo-propionic acid methyl ester and (2-Amino-phenyl)-(4-fluoro-phenyl)-meth-anone via condensation reactionbromination, reduction,phosphorus ylide forma-tion, Wittig reaction with t-butyl(3R,5S)3-6-oxo-3,5-dihydroxy-3,5-O-iso-pr-opylidenehexanoate in the presence of Hexamethyldisilazane sodium salt as the catalyst, and calcium salt was formed after deprotection. This route can be applied commercially.Result:Pitavastatin calcium is synthesized through ten steps with an total yield of 28.0%.Conclusion:Pitavastatin calcium obtained from this process is testified to be qualified API(Active Pharmaceutical Ingredients), so this Synthesis route is suitable for industrial production.