Title:
タペンタドールおよびその中間体を合成する新規のプロセス
Document Type and Number:
Japanese Patent JP5857044
Kind Code:
B2
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.
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Inventors:
Giuseppe Motta
Domenico Bergani
Giorgio Bertolini
Nicola Landoni
Domenico Bergani
Giorgio Bertolini
Nicola Landoni
Application Number:
JP2013517610A
Publication Date:
February 10, 2016
Filing Date:
June 20, 2011
Export Citation:
Assignee:
Uticals Societa Peratini
International Classes:
C07C213/02; C07C213/00; C07C215/54; C07C217/64; C07C219/22; C07C255/16
Domestic Patent References:
| JP2009544637A | ||||
| JP2010508240A | ||||
| JP2009544658A | ||||
| JP55098173A |
Other References:
薬学雑誌 YAKUGAKU ZASSHI,1972年,Vol. 92, No. 4,421-430
Attorney, Agent or Firm:
Patent Business Corporation Tani/Abe Patent Office