Preparation of rosuvastatin

A process for preparing rosuvastatin or a pharmaceutically acceptable salt thereof, comprising:

• a. providing a solution of Compound I of the following structure
• wherein Y is a C1-C4 ester, W is a carboxyl protecting group and X is a hydroxyl protecting group, and a polar solvent;
• b. combining the solution with a base to obtain a pH of about 10 to about 13 to form a first solution comprising Compound 17 of the following structure
• wherein W is a carboxyl protecting group and X is a hydroxyl protecting group;
• c. adding a second solution comprising a mono-, di-, tri-(C1 to C4) alkyl substituted benzene chloroformate, saturated or aromatic C5-C12 chloroformate or C1-8 alkyl chloroformate and an organic solvent to obtain a first reaction mixture while maintaining a temperature of about −50° C. to about −10° C.;
• d. maintaining the first reaction mixture for a sufficient period of time to obtain Compound 18 of the following structure
• wherein W is a carboxyl protecting group, X is a hydroxyl protecting group and Z is a C1-8 alkyl or aryl;
• e. providing a dry solvent and Compound 19A of the following structure
• wherein W is a carboxyl protecting group, T1 and T2 are independently aryl or alkoxy, and X is a hydroxyl protecting group;
• f. combining a base with the dry solvent and the Compound 19A to obtain a second reaction mixture;
• g. combining Compound 14 with the second reaction mixture at a reduced temperature to obtain a third reaction mixture;
• h. maintaining the third reaction mixture for a sufficient time to obtain the Compound 20;
• wherein W is a carboxyl protecting group and X is a hydroxyl protecting group;
• i. optionally, quenching the reaction;
• j. converting Compound 20 into Compound 21 of the following structure
• wherein W is a carboxyl protecting group;
• k. optionally recovering Compound 21 by providing a two-phased system comprised of a mixture of a non-polar aliphatic solvent and a non-polar aromatic solvent and a mixture of a mixture of a lower aliphatic alcohol and water, each in an amount of about 4 to about 6 volumes relative to Compound 21 and crude Compound 21, washing the non-polar phase with a mixture of lower aliphatic alcohol and water, and recovering Compound 21 from the organic phase;
• l. optionally crystallizing Compound 21;
• m. converting Compound 21 into Compound 22 of the following structure
• wherein W is a carboxyl protecting group;
• and
• n. converting Compound 22 into rosuvastatin.