A Practical Synthesis of Rosuvastatin and Other Statin Intermediates

The efficient aldol condensation between a derivative of methyl 3‐hydroxy‐5‐oxohexanoate and a pyrimidinecarbaldehyde comprising the core structure of rosuvastatin has been developed as an alternative approach to the classical methods employing ylides for the synthesis of rosuvastatin. The formation of a double bond connecting the aromatic part with the side chain of the statin was effectively promoted by using a strong Lewis acid which provided the optimum result in combination with a tertiary amine. The method was also successfully applied to the synthesis of pitavastatin. A new synthetic approach to statins has been developed. The efficient aldol condensation of heterocyclic aldehydes comprising the core structure of rosuvastatin and pitavastatin with a derivative of methyl 3‐hydroxy‐5‐oxohexanoate affords products with the desired E geometry in high yield.