The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jul. 29, 2014
Filed:
Jun. 20, 2011
Giuseppe Motta, Rescaldina, IT;
Domenico Vergani, Biassono, IT;
Giorgio Bertolini, Sesto San Giovanni, IT;
Nicola Landoni, Legnano, IT;
Giuseppe Motta, Rescaldina, IT;
Domenico Vergani, Biassono, IT;
Giorgio Bertolini, Sesto San Giovanni, IT;
Nicola Landoni, Legnano, IT;
Euticals S.p.A., Milan, IT;
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 forms I and II of the tapentadol free base.