| abstract |
The object of the present invention is a new process for the synthesis of tapentadol, both as a free base and in the form of hydrochloride, which comprises the stage of the alkylation of the ketone (VII) to produce the compound (VIII), as It is reported in diagram 1, with high stereoselectivity due to the presence of the benzyl group as a substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol balance 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 in the carbonyl towards the desired stereoisomer. This substitution, therefore, allows to obtain a considerable increase of the productions at this stage, and therefore, allows to significantly increase the total production of the whole 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 mixing of the crystalline forms I and II of the tapentadol free base. |