The Use of a Lactonized Statin Side-Chain Precursor in a Concise and Efficient Assembly of Pitavastatin
Zdenko Časar, Jan Fabris, Ivana Gazić Smilović · Synthesis · 2012
A concise and simple synthetic route to pitavastatin is described. The approach involves a highly stereoselective Wittig olefination reaction between a lactonized statin side-chain precursor and the triphenylphosphonium bromide salt of the corresponding quinoline heterocyclic core. The necessary O - tert -butyl(dimethyl)silyl-protected pitavastatin lactone was obtained in 75% yield and high purity by simple crystallization from aqueous methanol. Subsequent deprotection, hydrolysis, and cation exchange in a one-pot operation provided pitavastatin calcium in 93% yield.