Process for the synthesis of tapentadol and intermediates thereof
US8791287B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Jun 20, 2011 |
| Grant date | Jul 29, 2014 |
| Priority date | — |
| Expiry date | Jun 20, 2031 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07B2200/07
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process.A further object of the present invention is constituted by the tapentadol free base in solid form, obtainable by means of the process of the invention.Still another object of the invention is represented by the crystalline forms I and II of the tapentadol free base.A further object of the present invention is the mixture of the crystalline…
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.