Process for the preparation of enantiomerically pure amines
The present invention relates to an improved process for the preparation of (R)-1-aminoindan (2), rasagiline (1) and pharmaceutically acceptable salts of rasagiline.
1. A process for the preparation of enantiomerically pure (R)-1-aminoindan (2) comprising the formation of a diastereomeric salt of 1-aminoindan with 2,3,4,6-di-O-isopropylidene-2-keto-L-gulonic acid.
2. A process according to claim 1 , wherein the salt formation takes place in an organic solvent or a mixture of an organic solvent and water.
3. A process according to claim 1 , wherein the organic solvent is a C 1 -C 6 alcohol.
4. A process according to claim 3 , wherein the organic solvent is selected from the group comprising methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol and mixtures thereof.
5. A process according to claim 4 , wherein the organic solvent is methanol or a mixture of methanol and water.
6. A process according to claim 1 , wherein the diastereomeric salt formed is recrystallised.
7. A process according to claim 6 , wherein the diastereomeric salt formed is recrystallised from an organic solvent or water or a mixture thereof.
8. A process according to claim 7 , wherein the diastereomeric salt formed is recrystallised from a mixture of an organic solvent and water.
9. A process according to claim 7 , wherein the organic solvent is a C 1 -C 6 alcohol.
10. A process according to claim 9 , wherein the organic solvent is selected from the group comprising methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol and mixtures thereof.
11. A process according to claim 10 , wherein the diastereomeric salt formed is recrystallised from a mixture of methanol and water.
12. A process according to claim 11 , wherein the methanol to water ratio is between from about 1:0.75 to 1:1.5.
13. A process according to claim 1 , wherein the (R)-1-aminoindan (2) formed is converted to rasagiline (1) or a pharmaceutically acceptable salt thereof.
14. A process according to claim 13 , wherein the pharmaceutically acceptable salt is a mesylate salt.