Back to results
US 2007/0179166 A1Published application
Process for preparation of statins with high syn to anti ratio
OwnerValerie Niddam-Hildesheim, Anna Balanov +1inventors
InventorsValerie Niddam-Hildesheim, Anna Balanov, Kobi Chen
Life of this patent
Estimating the term…
Abstract
Provided is a process for reduction of statin ketoesters and purification of diol esters of the statins through selective crystallization.
Claims39
A process for preparing rosuvastatin diol ester comprising the steps of
- a) combining B-Methoxy-9-BBN, an organic solvent, and a ketoester having the formula:
- wherein R1 is a straight or branched C1 to C4 alkyl group, and wherein at least one X forms a double bond to give a ketone, and at most one X is a hydrogen, to obtain a reaction mixture,
- b) combining a source of hydride ions with the reaction mixture, and
- c) maintaining the reaction mixture to obtain the rosuvastatin diol ester.
1 more element
A process for preparing rosuvastatin from a rosuvastatin diol-ester having the formula:
- wherein R1 is a straight or branched C1 to C4 alkyl group;
- comprising the steps of
- a) combining a ketoester of rosuvastatin having the formula:
- with a solvent to form a solution, wherein R1 is a straight or branched C1 to C4 alkyl group, and wherein at least one X forms a double bond to give a ketone, and at most one X is a hydrogen;
- b) cooling the solution to a temperature of about −50° C. to about −80° C.;
- c) combining B-Methoxy-9-BBN with the solution to obtain a reaction mixture, and maintaining the reaction mixture for at least about 30 minutes;
- d) combining a source of hydride ions with the reaction mixture, and maintaining the reaction mixture for an additional period of at least about 2 hours;
- e) quenching the reaction mixture;
- f) recovering the rosuvastatin diol-ester;
- and
- g) converting the rosuvastatin diol-ester to rosuvastatin or a pharmaceutically acceptable salt of rosuvastatin.
8 more elements
A process for preparing rosuvastatin from a rosuvastatin ketoester having the formula:
- wherein R1 is a straight or branched C1 to C4 alkyl group, and wherein at least one X forms a double bond to give a ketone, and at most one X is a hydrogen, comprising the steps of
- a) combining the ketoester of rosuvastatin with a solvent to form a solution;
- b) cooling the solution to a temperature of about −50° C. to about −80° C.;
- c) combining B-Methoxy-9-BBN with the solution to obtain a reaction mixture and maintaining the reaction mixture for at least about 30 minutes;
- d) combining a source of the hydride ions to the reaction mixture and maintaining the reaction mixture for an additional period of at least about 2 hours to obtain rosuvastatin diol ester;
- e) quenching the reaction mixture;
- f) combining the rosuvastatin diol ester with NaOH or Ca(OH)2 and a solvent or a mixture of solvent and water;
- and
- g) recovering the rosuvastatin free acid, lactone or a pharmaceutically acceptable salt thereof.
6 more elements
Dependencies are inferred from the claim text.