Process for preparing 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one and ondansetron therefrom
AssigneeTaro Pharmaceutical Industries Ltd.
InventorsDaniella Gutman, Rosa Cyjon
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Abstract
The present invention provides a rapid, high-yielding process for preparing 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one from 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one without using a secondary amine as a catalyst, and without using glacial acetic acid as a solvent. The present invention further provides a rapid, high-yielding process for preparing ondansetron from 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one without using alumina as a catalyst.
Claims25
A process for preparing 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one, comprising the steps of:
- (a) preparing a mixture of 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one, a formaldehyde reagent, and a mineral acid in an aprotic solvent;
- (b) heating the mixture for about 1 hour to about 8 hours to provide 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one;
- and
- (c) isolating the 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one.
A process for preparing ondansetron, comprising the steps of:
- (a) preparing a mixture of 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one and 2-methylimidazole in toluene, with the proviso that the mixture does not contain alumina;
- (b) heating the mixture for about 1 hour to about 8 hours to provide ondansetron;
- and
- (c) isolating the ondansetron.
A process for preparing ondansetron, comprising the steps of:
- (a) preparing a first mixture of 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one, a formaldehyde reagent, and a mineral acid in an aprotic solvent;
- (b) heating the first mixture for about 1 hour to about 8 hours to provide 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one;
- (c) isolating the 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one;
- (d) preparing a second mixture of the isolated 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one and 2-methylimidazole in toluene, with the proviso that the second mixture does not contain alumina;
- (e) heating the second mixture for about 1 hour to about 8 hours to provide ondansetron;
- and
- (f) isolating the ondansetron.
Dependencies are inferred from the claim text.