| Autor: |
Hayler, J. D., Howie, S. L. B., Giles, R. G., Negus, A., Oxley, P. W., Walsgrove, T. C., Whiter, M. |
| Zdroj: |
Organic Process Research & Development; January 1998, Vol. 2 Issue: 1 p3-9, 7p |
| Abstrakt: |
Two plant syntheses of ropinirole {4-[2-(di-n-propylamino)ethyl]-1,3-dihydro-2H-indolin-2-one hydrochloride, SK&F-101468-A} using the ferric chloride mediated cyclisation of β-nitrostyrenes to form 3-chlorooxindoles as the key step are described. The first synthesis suffered the severe limitation of the final-step chemistry being nonselective in the reaction between di-n-propylamine and the bromide precursor to ropinirole as both substitution and elimination pathways were promoted and by-product formation at a level of 40% resulted. This problem was rectified in the latter synthesis by the more selective reaction between di-n-propylamine and the sulfonate ester precursor promoting ropinirole formation to a level of 88%. This second synthesis is now used as the commercial route, and problems (and their solutions) identified during the development of this route are now described. The identification of novel by-products which enabled the Sommelet oxidation step to be optimised is also reported. A unimolecular decomposition mechanism during hydrolysis of the hexaminium salt to form the key benzaldehyde intermediate is proposed and substantiated with experimental data. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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