Process for preparation of rosuvastatin calcium

A process for producing rosuvastatin calcium salt comprising:

• a) combining a suspension of t-butyl ester of rosuvastatin in ethanol with sodium hydroxide to obtain a solution, and stirring during or after the combining;
• b) evaporating the solution under reduced pressure to obtain a residue;
• c) combining the residue with water to obtain an aqueous solution;
• d) washing the aqueous solution with ethyl acetate;
• e) evaporating traces of the ethyl acetate under reduced pressure;
• f) adding calcium chloride to the solution to precipitate rosuvastatin calcium;
• and
• g) filtering the rosuvastatin calcium salt.

A process for producing rosuvastatin calcium salt comprising:

• a) reacting a C1 to C4 alkyl ester of rosuvastatin in a water immiscible phase, with a base in an aqueous phase, in presence of a phase transfer catalyst to obtain rosuvastatin in the aqueous phase;
• b) adding a source of calcium to the aqueous phase to precipitate rosuvastatin calcium;
• and
• c) recovering the rosuvastatin calcium salt;
• with the proviso that:
• (i) the process further comprising a step of removing traces of the water immiscible solvent before adding a source of calcium;
• wherein the ester is a t-butyl ester:
• (ii) the process further comprises stirring during the reaction;
• (iii) wherein the water immiscible phase is a solvent selected from the group consisting of substituted and unsubstituted C5 to C12 hydrocarbon, C4 to C7 ester, C4 to C7 ketone and mixtures thereof;
• or
• (iv) the hydrocarbon is toluene or chlorobenzene.

A process for producing rosuvastatin calcium salt comprising:

• a) reacting, t-butyl ester of rosuvastatin with sodium hydroxide in presence of water, a tetrabutylammonium phase transfer catalyst and an organic solvent selected from the group consisting of toluene and chlorobenzene to obtain rosuvastatin in the water;
• b) removing traces of the toluene or chlorobenzene from the water;
• c) adding calcium chloride to the water to precipitate rosuvastatin calcium;
• and
• d) filtering the rosuvastatin calcium salt.

A process for producing rosuvastatin calcium salt substantially free of impurities comprising the steps of:

• a) reacting a C1 to C4 ester of rosuvastatin with a base in a two phase system of water and acetonitrile;
• b) concentrating the water phase to obtain a residue;
• c) adding a source of calcium and water to the residue to form a solution in water;
• and
• d) recovering rosuvastatin calcium as a precipitate.

A process for producing rosuvastatin calcium comprising:

• a) preparing a solution of rosuvastatin sodium;
• b) concentrating the solution to obtain a residue;
• c) combining the residue with water to obtain an aqueous solution;
• d) washing the aqueous solution with a water immiscible organic solvent;
• e) removing traces of the organic solvent;
• f) adding a source of calcium to the solution to precipitate rosuvastatin calcium;
• and
• g) recovering the rosuvastatin calcium salt.