Synthesis and characterization of Rosuvastatin calcium impurity A; a HMG-CoA reductase inhibitor

Abstract

During the process development for multistep synthesis of Rosuvastatin calcium several impurities were obtained along with the final Rosuvastatin calcium. Out of this; synthesis of impurity A (acetone adduct) a minor impurity of Rosuvastatin calcium (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[[(2-hydroxy-2-methyl-propyl)sulfonyl(methyl)amino]-6-(1-methylethyl)-pyrimidin-5-y1]-3,5-dihydroxyheptenoicacid hemicalcium salt, is described. The synthesis of impurity A has been accomplished in 6 steps; starting from formation of beta-hydroxy sulfonamide as the key intermediate and followed by using convenient routes with overall yield of 13.5%. The target compound can be used as the reference substance of impurity of the Rosuvastatin calcium. (C) 2017 Elsevier Ltd. All rights reserved.