Process for preparing simvastatin having controlled ranges of simvastatin dimer content
OwnerFerenc Korodi, Csaba Szabo +2inventors
InventorsFerenc Korodi, Csaba Szabo, Szabolcs Salyi, Istvan Bodi
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Abstract
The present invention relates to a process for preparing simvastatin, wherein the simvastatin dimer content is controlled. More particularly, the present invention relates to a process for preparing simvastatin having a simvastatin dimer content of about 0.2 to about 0.4 % wt. The present invention also relates to a process for preparing simvastatin having a simvastatin dimer content of less than about 0.2% wt. The present invention also discloses a commercial scale process of preparing simvastatin having a specified simvastatin dimer content which is reproducible.
Claims5
A process for preparing simvastatin with a specified simvastatin dimer content, comprising the steps of:
- a) lactonizing an ammonium salt of simvastatin in aromatic hydrocarbon at a concentration of less than about 60 g/l to form a simvastatin;
- b) dissolving the simvastatin in at least one solvent selected from the group consisting of toluene, ethylacetate, tetrahydrofuran, and benzene and precipitating the dissolved simvastatin with an anti-solvent selected from the group consisting of pentane, hexane, heptane, cyclohexane and petroleum ether;
- c) isolating the crystallized simvastatin;
- d) dissolving the crystallized simvastatin in at least one solvent selected from the group consisting of toluene, ethylacetate, tetrahydrofuran, and benzene and precipitating the dissolved simvastatin with an anti-solvent selected from the group consisting of pentane, hexane, heptane, cyclohexane and petroleum ether;
- e) isolating the recrystallized simvastatin;
- f) dissolving the simvastatin obtained in step e) in a water miscible organic solvent selected from the group consisting of methanol, ethanol, acetone, acetonitrile and tetrahydrofuran;
- and
- g) adding an anti-solvent to induce precipitation to obtain recrystallized simvastatin,
- wherein the recrystallized simvastatin contains a simvastatin dimer content of less than 0.2% wt.
A process for preparing simvastatin with a specified simvastatin dimer content, comprising the steps of:
- a) lactonizing an ammonium salt of simvastatin in toluene at a concentration of less than about 60 g/l to form a simvastatin;
- b) dissolving the simvastatin in toluene and precipitating the dissolved simvastatin with hexane;
- c) isolating the crystallized simvastatin;
- d) dissolving the crystallized simvastatin in toluene and precipitating the dissolved simvastatin with hexane;
- e) isolating the recrystallized simvastatin;
- f) dissolving the simvastatin obtained in step e) in methanol;
- and
- g) adding water to induce precipitation to obtain recrystallized simvastatin,
- wherein the recrystallized simvastatin contains a simvastatin dimer content of less than 0.2% wt.
Dependencies are inferred from the claim text.