[go: up one dir, main page]

US20060167318A1 - Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)- amine compounds by heterogeneous catalysis - Google Patents

Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)- amine compounds by heterogeneous catalysis Download PDF

Info

Publication number
US20060167318A1
US20060167318A1 US11/313,937 US31393705A US2006167318A1 US 20060167318 A1 US20060167318 A1 US 20060167318A1 US 31393705 A US31393705 A US 31393705A US 2006167318 A1 US2006167318 A1 US 2006167318A1
Authority
US
United States
Prior art keywords
alkyl
compound
catalyst
reaction
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/313,937
Other languages
English (en)
Inventor
Utz-Peter Jagusch
Wolfgang Hoelderich
Monika Wissler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gruenenthal GmbH
Original Assignee
Gruenenthal GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gruenenthal GmbH filed Critical Gruenenthal GmbH
Assigned to GRUENENTHAL GMBH reassignment GRUENENTHAL GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: JAGUSCH, UTZ-PETER, WISSLER, MONIKA, HOELDERICH, WOLFGANG
Publication of US20060167318A1 publication Critical patent/US20060167318A1/en
Priority to US13/667,110 priority Critical patent/US8704002B2/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to a process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and to processes for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis.
  • Opioids for example morphine
  • Opioids have been used in the therapy of pain for many years, although they cause a number of side-effects, for example addiction, dependency, respiratory depression, impaired gastro-intestinal motility and constipation. They can therefore be taken for a prolonged period and in relatively high doses only with particular safety measures (Goodman, Gilman, The Pharmacological Basis of Therapeutics, Pergamon Press, New York 1990).
  • a further class of active ingredients having excellent analgesic effectiveness and very good tolerability are the substituted dimethyl-(3-aryl-butyl)-amine compounds, which are known inter alia from EP 0 693 475.
  • the preparation of these pharmaceutical active ingredients is likewise carried out starting from tertiary alcohols, which are first converted into the corresponding chloride compound and then reduced with zinc borohydride, zinc cyanoborohydride or tin cyanoborohydride.
  • This process has the disadvantage that the preparation of the chloride compound is carried out with the use of comparatively aggressive chlorinating agents such as thionyl chloride. Furthermore, the process does not give a satisfactory yield in all cases.
  • the object of the present invention was, therefore, to provide a process for removing the tertiary alcohol function from substituted 4-dimethylamino-2-aryl-butan-2-ol compounds, with which process the correspondingly substituted dimethyl-(3-aryl-but-3-enyl)-amine compounds are obtained in good yields under environmentally protective conditions and whereby it is also possible to prepare correspondingly substituted dimethyl-(3-aryl-butyl)-amine compounds in good yields with a simplified procedure.
  • this object is achieved by the provision of the processes described hereinbelow for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds of the general formula I below and for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds of the general formula III below, optionally with isolation of substituted dimethyl-(3-aryl-but-3-enyl) compounds of the general formula II below.
  • the compounds of the general formulae II and III are preferably used as pharmaceutical active ingredients in medicaments and are suitable in particular for controlling pain.
  • substituted dimethyl-(3-aryl-but-3-enyl)-amine compounds of the general formula II obtained by the above-described process can be reacted according to conventional processes known to the person skilled in the art to form substituted dimethyl-(3-aryl-butyl)-amine compounds of the general formula III below.
  • the present invention further provides a process for the preparation of at least one substituted dimethyl-(3-aryl-butyl)-amine compound of the general formula III wherein the radicals R 1 , R 1′ , R 2 , R 3 , R 4 , R 4′ , R 5 , R 5′ and R 6 are each as defined above, in each case in the form of one of their pure stereoisomers, in particular enantiomers or diastereoisomers, of their racemates or in the form of a mixture of stereoisomers, in particular of enantiomers or diastereoisomers, in any desired mixing ratio, or in each case in the form of a physiologically acceptable salt, or in each case in the form of a solvate, according to which process at least one substituted 4-dimethylamino-2-aryl-butan-2-ol compound of the general formula I wherein the radicals R 1 , R 1′ , R 2 , R 3 , R 4 , R 4′ , R
  • R 1 is C 1-5 -alkyl
  • R 2 represents H or C 1-5 -alkyl
  • R 3 represents H or C 1-5 -alkyl
  • R 4 is H, OH, C 1-4 -alkyl, O-C 1-4 -alkyl, O-benzyl, CF 3 , O—CF 3 , Cl, F or OR 8
  • R 5 is H, OH, C 1-4 -alkyl, O-C 1-4 -alkyl, O-benzyl, CHF 2 , CF 3 , O—CF 3 , Cl, F or OR 8
  • R 6 represents H, OH, C 1-4 -alkyl, O-C 1-4 -alkyl, O-benzyl, CF 3 , O—CF 3 , Cl, F or OR 8 , with the proviso that two of
  • R 1 is C 1-3 -alkyl
  • R 2 is H or C 1-3 -alkyl
  • R 3 is H or C 1-3 -alkyl
  • R 4 is H, OH, Cl, F or OR 8 ,
  • R 5 is H, OH, C 1-4 -alkyl, O-C 1-4 -alkyl, O-benzyl, CHF 2 , CF 3 , Cl, F or OR 8 ,
  • R 6 is H, OH, O-C 1-4 -alkyl, O-benzyl, CF 3 , Cl, F or OR 8 ,
  • R 8 to R 10 are as defined above.
  • R 1 is CH 3 or C 3 H 7 ,
  • R 2 is H, CH 3 or CH 2 CH 3 ,
  • R 3 is H, CH 3 or CH 2 CH 3 ,
  • R 4 is H or OH
  • R 5 is H, OH, OCH 3 , CHF 2 or OR 8 ,
  • R 6 is H, OH or CF 3 ,
  • R 4 , R 5 or R 6 are H; or R 4 and R 5 together represent a group —CH ⁇ C(CH 3 )—S— as part of a ring, and R 6 is H; or R 5 and R 6 together represent —CH ⁇ CH—C(OH) ⁇ CH— as part of a ring, and R 4 is H,
  • R 8 represents CO—C 6 H 4 —R 11 and R 11 represents —OC(O)—C 1-3 -alkyl in the ortho-position.
  • substituted 4-dimethylamino-2-aryl-butan-2-ol compounds can be prepared by conventional processes known to the person ordinarily skilled in the art, as described, for example, in EP 0 693 475 and EP 0 799 819, the corresponding descriptions of which are incorporated herein by reference and form part of the disclosure.
  • substituted dimethyl-(3-aryl-but-3-enyl)-amine compounds obtained by dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds are, where appropriate, usually in the form of a mixture of their stereoisomers. These can be separated from one another by conventional methods known to the person ordinarily skilled in the art, for example by means of chromatographic methods.
  • the reaction of the substituted dimethyl-(3-aryl-but-3-enyl)-amine compounds of the general formula II to form substituted dimethyl-(3-aryl-butyl)-amine compounds of the general formula III optionally likewise leads to a mixture of different stereoisomers, which can be separated from one another by conventional methods known to the person ordinarily skilled in the art. Examples which may be mentioned include chromatographic separation processes, in particular liquid chromatography processes under normal pressure or under elevated pressure, preferably MPLC and HPLC processes, as well as processes of fractional crystallisation. It is thereby possible in particular to separate from one another individual enantiomers, e.g.
  • substituted 4-dimethylamino-2-aryl-butan-2-ol compounds of the general formula I can be used in the processes according to the invention in each case both in the form of their bases, their acids and in each case in the form of their salts or in each case in the form of corresponding solvates, preferably hydrates.
  • the salt can preferably be selected from the group consisting of chloride, bromide, sulfate, sulfonate, phosphate, tartrate, teoclate, embonate, formate, acetate, propionate, benzoate, oxalate, succinate, citrate, diclofenacate, naproxenate, salicylate, acetylsalicylate, glutamate, fumarate, aspartate, glutarate, stearate, butyrate, malonate, lactate, mesylate, saccharinate, cyclamate and acesulfamate, particularly preferably from the group consisting of chloride, sulfate,
  • the salts are usually in the form of a corresponding acid addition salt, for example in the form of the hydrochloride.
  • substituted dimethyl-(3-aryl-but-3-enyl)-amine compounds of the general formula II or the substituted dimethyl-(3-aryl-butyl)-amine compounds of the general formula III are obtained by the processes according to the invention in the form of their bases, they can be converted into the corresponding salts, preferably into one of the salts listed above, by conventional processes known to the person ordinarily skilled in the art.
  • Heterogeneous catalysis within the context of the present invention means that the catalysts used in the processes according to the invention are in each case present in the solid state of aggregation.
  • catalyst within the context of the present invention includes both catalytically active materials themselves and inert materials that are provided with a catalytically active material. Accordingly, the catalytically active material can, for example, be applied to an inert carrier or can be present in a mixture with an inert material. There come into consideration as inert carrier or inert material, for example, carbon and other materials known to the person skilled in the art.
  • the substituted 4-dimethylamino-2-aryl-butan-2-ol components or the substituted dimethyl-(3-aryl-but-3-enyl)-amine components used in the processes according to the invention are preferably in liquid phase and to that end are preferably mixed with or dissolved in a reaction medium that is liquid under the particular reaction conditions.
  • reaction media examples include water or organic liquids such as halogenated organic compounds, alcohols or ketones, preferably dichloromethane, chloroform, toluene or methanol, particularly preferably acetone or especially ethanol.
  • halogenated organic compounds preferably dichloromethane, chloroform, toluene or methanol, particularly preferably acetone or especially ethanol.
  • mixtures or multiphase systems comprising two or more of the above-mentioned liquids in the processes according to the invention.
  • a reaction in supercritical CO 2 as solvent is also possible.
  • the dehydration of the substituted 4-dimethylamino-2-aryl-butan-2-ol compounds of the general formula I is preferably carried out in the presence of at least one acidic catalyst and/or at least one basic catalyst, particularly preferably in the presence of at least one acidic catalyst. It is also possible to use catalysts that have been provided with both acidic and basic properties.
  • Suitable acidic and/or basic catalysts can preferably be selected from the group consisting of ion-exchange resins, zeolites, heteropoly acids, phosphates, sulfates and optionally mixed metal oxides.
  • the dehydration is preferably carried out in the presence of at least one acidic catalyst, which can preferably be selected from the group consisting of ion-exchange resins, zeolites, heteropoly acids, phosphates, sulfates and optionally mixed metal oxides.
  • at least one acidic catalyst which can preferably be selected from the group consisting of ion-exchange resins, zeolites, heteropoly acids, phosphates, sulfates and optionally mixed metal oxides.
  • Suitable catalysts and their preparation are known per se to the person skilled in the art, for example from Venuto, P. B., Microporous Mater., 1994, 2, 297; Hölderich, W. F., van Bekkum, H., Stud. Surf. Sci. Catal., 1991, 58, 631, Hölderich, W. F., Proceedings of the 10th International Congress on Catalysis, 1992, Budapest, Guczi, L. et al. (editors), “New Frontiers in Catalysis”, 1993, Elsevier Science Publishers, Kozhenikov, I. V., Catal. Rev. Sci. Eng., 1995, 37, 311, Song, X., Sayari, A., Catal. Rev. Sci. Eng., 1996, 38, 329. The corresponding literature descriptions are incorporated herein by reference and form part of the disclosure.
  • ion-exchange resins based on tetrafluoroethylene/perfluorovinyl ether copolymers, optionally in the form of their silica nanocomposites, as are described, for example, in the literature publications of Olah et al. Synthesis, 1996, 513-531 and Harmer et al. Green Chemistry, 2000, 7-14, the corresponding descriptions of which are incorporated herein by reference and form part of the disclosure.
  • ion-exchange resins based on styrene/divinylbenzene copolymers which can be prepared by conventional processes known to the person skilled in the art.
  • sulfonic-acid-group-carrying ion-exchange resins based on styrene/divinylbenzene copolymers, as are marketed, for example, under the trade name Amberlyst® by Rohm & Haas and which can also be used as such in the processes according to the invention.
  • ion-exchange resins are distinguished in particular by their stability towards water and alcohols, even at elevated temperatures, for example from 130 to 160° C.
  • the degree of crosslinking and the structure of these ion-exchange resins can vary.
  • the macroporous resins in particular can be used with particular advantage for heterogeneous catalysis in the liquid phase.
  • Particularly suitable macroporous resins having a mean pore diameter of from about 20 to about 30 nm and a minimum concentration of active groups of from about 4.70 to about 5.45 equivalents per kg of resin are available commercially under the trade names Amberlyst® 15, Amberlyst® 35 and Amberlyst® 36 and accordingly can also be used in the processes according to the invention.
  • an acidic catalyst based on metal oxides such as, SiO 2 , Al 2 O 3 , TiO 2 , Nb 2 O 5 , B 2 O 3 or based on mixed metal oxides such as, Al 2 O 3 /SiO 2 or Al 2 O 3 /B 2 O 3 .
  • reaction parameters for the processes according to the invention for example, pressure, temperature or reaction time, can vary over a wide range.
  • the temperature during these reactions is in each case from about 20 to about 250° C., particularly preferably from about 50 to about 180° C. and very particularly preferably from about 100 to about 160° C.
  • Both reactions can be carried out at reduced pressure, at normal pressure or at elevated pressure, preferably in the range from about 0.01 to about 300 bar. It is particularly preferred to carry out the reactions under pressure in a range from about 2 to about 10 bar, in particular from about 4 to about 8 bar.
  • the reaction time can vary in dependence on various parameters, for example, temperature, pressure, nature of the compound to be reacted or the properties of the catalyst, and can be determined for the process in question by the person skilled in the art using preliminary tests.
  • the ratio of catalyst and compound to be reacted is preferably in the range from about 1:200 to about 1:1, in particular from about 1:4 to about 1:2.
  • the catalyst can be separated from the reaction mixture in a simple manner, preferably by filtration.
  • the particular substituted dimethyl-(3-aryl-but-3-enyl)-amine compound of the general formula II obtained as intermediate or end product can be isolated and/or purified by conventional methods known to the person skilled in the art.
  • the reaction of the substituted dimethyl-(3-aryl-but-3-enyl)-amine compound of the general formula II obtained as intermediate is carried out by heterogeneously catalysed hydrogenation with hydrogen.
  • the hydrogen is preferably in gaseous form, although it is also possible for at least part of it to be dissolved in a liquid phase.
  • reaction of the dimethyl-(3-aryl-but-3-enyl)-amine compounds of the general formula II obtained as intermediate with heterogeneous catalysis is preferably carried out in the presence of at least one catalyst that contains one or more transition metals, and optionally in the presence of at least one of the catalysts used above for the dehydration.
  • this reaction it is also possible for this reaction to be carried out in the presence of at least one of the polyfunctionalized, preferably bifunctionalized, catalysts described hereinbelow.
  • the dehydration to form the intermediate and its reaction or purification and/or isolation to form the end product are preferably carried out in the presence of at least one polyfunctionalized, preferably bifunctionalized, catalyst.
  • bi- or poly-functionalized catalysts are understood as being those catalysts that have two or more different functionalities and therefore are able to accelerate two or more different reactions, preferably at least the dehydration and the subsequent reaction of the intermediate so obtained.
  • bifunctional catalysts that are acidic and/or basic, preferably acidic, and contain at least one transition metal.
  • Such bifunctionaliszd catalysts are particularly preferably derived from one of the, catalysts mentioned above preferably acidic, for the dehydration.
  • these metals can preferably be selected from the group consisting of Cu, Ag, Au, Zn, Cd, Hg, V, Nb, Ta, Cr, Mo, W, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, and Pt, particularly preferably from the group consisting of Ru, Rh, Pd, Os, Ir and Pt, and very particularly preferably from the group consisting of Pd, Ru, Pt and Ir. Palladium is most preferred.
  • the corresponding catalysts can preferably contain one or more of the above-mentioned transition metals in the same or different oxidation states. It may also be preferable for the corresponding catalysts to contain one or more of the above-mentioned transition metals in two or more different oxidation states.
  • catalysts doped with transition metals can be carried out by conventional processes known to the person ordinarily skilled in the art.
  • the present invention further provides a process for the preparation of at least one substituted dimethyl-(3-aryl-butyl)-amine compound of the general formula III wherein the radicals R 1 , R 1′ , R 2 , R 3 , R 4 , R 4′ , R 5 , R 5′ and R 6 are as defined above, in each case in the form of one of their pure stereoisomers, in particular enantiomers or diastereoisomers, of their racemates or in the form of a mixture of stereoisomers, in particular of enantiomers or diastereoisomers, in any desired mixing ratio, or in each case in the form of a physiologically acceptable salt, or in each case in the form of a solvate, characterized in that at least one substituted dimethyl-(3-aryl-but-3-enyl)-amine compound of the general formula II wherein the radicals R 1 , R 1′ , R 2 , R 3 , R 4 , R 4′ , R 5
  • the process according to the invention is particularly suitable for preparing a mixture of ( ⁇ )-(2R,3R)-[3-(3-methoxy-phenyl)-2-methyl-pentyl]-dimethylamine and ( ⁇ )-(2R, 3S)-[3-(3-methoxy-phenyl)-2-methyl-pentyl]-dimethylamine from ( ⁇ )-(2S, 3S)-1-dimethylamino-3-(3-methoxy-phenyl)-2-methyl-pentan-3-ol.
  • reaction parameters for the processes according to the invention can vary over a wide range both in the dehydration of the substituted 4-dimethylamino-2-aryl-butan-2-ol compounds of the general formula I and in the reaction of the substituted dimethyl-(3-aryl-but-3-enyl) compounds of the general formula II.
  • the temperature during these reactions is in each case from 20 to 250° C., particularly preferably from about 50 to about 180° C. and very particularly preferably from about 100 to about 160° C.
  • Both reactions can be carried out at reduced pressure, at normal pressure or at elevated pressure, preferably in the range from about 0.01 to about 300 bar. It is particularly preferred to carry out the reactions under pressure in a range from about 2 to about 10 bar, in particular from about 4 to about 10 bar.
  • the reaction time can vary in dependence on various parameters, such as, for example, temperature, pressure, nature of the compound to be reacted or the properties of the catalyst, and can be determined for the process in question by the person skilled in the art using preliminary tests.
  • the amount of the catalyst(s) used depends on various factors, such as, the ratio of the catalytically active component to any inert material present, or the nature of the surface of the catalyst.
  • the optimal amount of catalyst for a particular reaction can be determined by the person skilled in the art using preliminary tests.
  • the catalyst and the compound to be reacted can preferably be used in a ratio of from about 1:200 to about 1:1, particularly preferably from about 1:4 to about 1:2.
  • the processes according to the invention can each be carried out discontinuously (batchwise) or continuously, preferably with the discontinuous procedure.
  • reactors are suitable for the discontinuous procedure of the present invention, for example, a slurry reactor, and for the continuous procedure a fixed-bed reactor or loop reactor.
  • the solid catalysts used according to the invention can additionally be separated from the reaction mixture in a simple manner, optionally regenerated and used again.
  • a sulfonic-acid-group-carrying ion-exchange resin based on a styrene/divinylbenzene copolymer having a divinylbenzene content of 20 wt. %, based on the total weight of the resin, a mean pore diameter of 25 nm and a minimum concentration of active groups of 4.70 equivalents per kg of resin (Amberlyst® 15, Fluka, Switzerland) were suspended in 20 ml of water.
  • a palladium tetramine dinitrate hydrate solution having a palladium content of 69.5 mg/ml was then added, and stirring was carried out for 24 hours at a temperature of 80° C.
  • 10 g of palladium(II) nitrate dihydrate (Fluka) were added to 400 g of ammonia solution (25 wt. % in water) and the mixture so obtained was stirred for 3 days at 50° C. The undesired solid was then separated off by filtration, and the palladium content was determined by ICP-AES, as described in R.
  • the catalyst so obtained was then filtered off, washed with water and dried for 3-4 hours at 120° C. under a medium-high vacuum.
  • the finished product has a Pd content of 1 wt. %.
  • a sulfonic-acid-group-carrying ion-exchange resin based on a styrene/divinylbenzene copolymer having a divinylbenzene content of 12 wt. %, based on the total weight of the resin, a mean pore diameter of 20 nm and a minimum concentration of active groups of 5.45 equivalents per kg of resin (Amberlyst® 36, Fluka, Switzerland) were suspended in 20 ml of water.
  • a palladium tetramine dinitrate hydrate solution prepared according to Example 1a, having a palladium content of 69.5 mg/ml was then added, and stirring was carried out for 24 hours at a temperature of 80° C.
  • the catalyst so obtained was then filtered off, washed with water and dried for 3-4 hours at 120° C. under a medium-high vacuum.
  • the finished product has a Pd content of 1 wt. %.
  • the yield of [3-(3-methoxy-phenyl)-2-methyl-pentyl]-dimethyl-amine; hydrochloride (3) was >96% with a ratio of the enantiomer ( ⁇ )-(2R,3R) to the diastereoisomer ( ⁇ )-(2R,3S) of 76:24.
  • the ( ⁇ )-(2R,3R) enantiomer is preferably used as an active ingredient in medicaments.
  • the ethanol was first removed in a rotary evaporator and then the crude product so obtained was recrystallised from heptane:tetrahydrofuran in a ratio of 1:1 (volume/volume), yielding colourless crystals which were again analyzed by means of gas chromatography.
  • Example 4a The preparation was carried out analogously to Example 4a), the catalyst obtained according to Example 1b) being used instead of the catalyst obtained according to Example 1a).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
US11/313,937 2003-06-23 2005-12-22 Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)- amine compounds by heterogeneous catalysis Abandoned US20060167318A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US13/667,110 US8704002B2 (en) 2003-06-23 2012-11-02 Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10328316A DE10328316A1 (de) 2003-06-23 2003-06-23 Verfahren zur Herstellung von Dimethyl-(3-aryl-buthyl)-aminverbindungen als pharmazeutische Wirkstoffe
DE10328316.1 2003-06-23
PCT/EP2004/006666 WO2005000788A1 (fr) 2003-06-23 2004-06-21 Procede de deshydratation de composes 4-dimethylamino-2-aryl-butane-2-ol substitues, et procede de fabrication de composes dimethyl-(3-aryl-butyl)-amine substitues, par catalyse heterogene

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2004/006666 Continuation WO2005000788A1 (fr) 2003-06-23 2004-06-21 Procede de deshydratation de composes 4-dimethylamino-2-aryl-butane-2-ol substitues, et procede de fabrication de composes dimethyl-(3-aryl-butyl)-amine substitues, par catalyse heterogene

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/667,110 Continuation US8704002B2 (en) 2003-06-23 2012-11-02 Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis

Publications (1)

Publication Number Publication Date
US20060167318A1 true US20060167318A1 (en) 2006-07-27

Family

ID=33520871

Family Applications (2)

Application Number Title Priority Date Filing Date
US11/313,937 Abandoned US20060167318A1 (en) 2003-06-23 2005-12-22 Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)- amine compounds by heterogeneous catalysis
US13/667,110 Expired - Lifetime US8704002B2 (en) 2003-06-23 2012-11-02 Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis

Family Applications After (1)

Application Number Title Priority Date Filing Date
US13/667,110 Expired - Lifetime US8704002B2 (en) 2003-06-23 2012-11-02 Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis

Country Status (11)

Country Link
US (2) US20060167318A1 (fr)
EP (1) EP1636169B1 (fr)
CN (2) CN1809527B (fr)
AT (1) ATE469877T1 (fr)
DE (2) DE10328316A1 (fr)
ES (1) ES2345658T3 (fr)
IL (1) IL172692A (fr)
PL (1) PL1636169T3 (fr)
PT (1) PT1636169E (fr)
SI (1) SI1636169T1 (fr)
WO (1) WO2005000788A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090043132A1 (en) * 2005-11-02 2009-02-12 Gruenenthal Gmbh Process for Preparing a Substituted Dimethyl-(3-arylbutyl)amine Compound by Homogeneous Catalysis
US20090312578A1 (en) * 2006-07-24 2009-12-17 Filliers Walter Ferdinand Mari Preparation of (2r,3r)-3-(3-methoxyphenyl)-n,n,2-trimethylpentanamine
US20090326271A1 (en) * 2006-07-24 2009-12-31 Gruenenthal Gmbh Preparation of 3-[(1R,2R)-3-(Dimethylamino)-1Ethyl-2-Methylpropyl]phenol
US20100099916A1 (en) * 2006-07-24 2010-04-22 Gruenenthal Gmbh Process for the Preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol
US20110071120A1 (en) * 2009-09-22 2011-03-24 Actavis Group Ptc Ehf Solid state forms of tapentadol salts
WO2011157390A3 (fr) * 2010-06-15 2012-03-15 Grünenthal GmbH Procédé de préparation de composés 3-(1-amino-2-methylpentane-3-yl)phényle substitué
WO2012038974A1 (fr) 2010-09-20 2012-03-29 Ind-Swift Laboratories Limited Procédé de préparation de dérivés de l-phényl-3-diméthylaminopropane
WO2013105109A1 (fr) * 2011-11-09 2013-07-18 Indoco Remedies Limited Procédé de préparation de tapentadol
EP2674414A1 (fr) 2012-06-15 2013-12-18 Siegfried AG Appareils dýimpression
US8704002B2 (en) 2003-06-23 2014-04-22 Grünenthal GmbH Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis
WO2015075678A1 (fr) 2013-11-21 2015-05-28 Unimark Remedies Ltd. Nouveau procédé pour la préparation de dérivés de 1-phényl-3-aminopropane
US9090539B2 (en) 2013-05-24 2015-07-28 Ampac Fine Chemicals Llc Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds
US9914695B2 (en) 2015-07-10 2018-03-13 Mallinckrodt Llc Two-step process for preparing 3-substituted phenylalkylamines

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102002065B (zh) * 2009-09-02 2014-09-10 上海特化医药科技有限公司 他喷他多的制备方法及其中间体
US8410176B2 (en) 2009-12-29 2013-04-02 Mapi Pharma Ltd. Intermediate compounds and processes for the preparation of tapentadol and related compounds
US20130096346A1 (en) 2010-03-05 2013-04-18 Actavis Group Ptc Ehf Resolution methods for isolating desired enantiomers of tapentadol intermediates and use thereof for the preparation of tapentadol
WO2011128784A2 (fr) 2010-04-05 2011-10-20 Actavis Group Ptc Ehf Nouveau procédé de synthèse de tapentadol de pureté élevée ou de l'un de ses sels de qualité pharmaceutique
EP2595971A1 (fr) * 2010-07-23 2013-05-29 Grünenthal GmbH Sels ou co-cristaux de 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)- phénol
WO2012023147A1 (fr) 2010-08-16 2012-02-23 Indoco Remedies Limited Procédé de préparation de tapentadol
EP2545028A4 (fr) * 2011-01-27 2013-07-03 Symed Labs Ltd Synthèse stéréospécifique inédite du (-) (2s,3s)-1-diméthylamino-3-(3-méthoxyphényl)-2-méthylpentan-3-ole
WO2012146978A2 (fr) 2011-04-28 2012-11-01 Actavis Group Ptc Ehf Nouveau processus de préparation de tapentadol ou d'un sel pharmaceutiquement acceptable de ce dernier
WO2013090161A1 (fr) 2011-12-12 2013-06-20 Boehringer Ingelheim International Gmbh Synthèse stéréosélective du tapendatol et de ses sels
WO2013120466A1 (fr) 2012-02-17 2013-08-22 Zentiva, K.S. Nouvelle forme solide du tapentadol et procédé pour sa préparation
WO2015091068A1 (fr) 2013-12-16 2015-06-25 Farma Grs, D.O.O. Formes cristallines d'intermédiaire du tapentadol
CZ307492B6 (cs) 2014-02-04 2018-10-17 Zentiva, K.S. Pevná forma maleátu tapentadolu a způsob její přípravy
AU2015287663B2 (en) * 2014-07-10 2019-02-28 SpecGx LLC Process for preparing substituted phenylalkanes
JP7486438B2 (ja) * 2018-06-15 2024-05-17 ファーマシェン エス．エー． タペンタドールの調製のための新規な方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4012456A (en) * 1974-11-19 1977-03-15 Chaplits Donat N Method for separation of isobutylene from C4 hydrocarbon fractions
US4276195A (en) * 1979-12-20 1981-06-30 Iowa State University Research Foundation, Inc. Converting homogeneous to heterogeneous catalysts
US5811582A (en) * 1996-03-13 1998-09-22 Gruenenthal Gmbh Dimethyl-(3-aryl-but-3-enyl)-amine compounds as pharmaceutical active ingredients

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE791133A (fr) * 1971-11-10 1973-05-09 Calgon Corp Nouveaux monomeres cationiques et leurs procedes de fabrication
AT322534B (de) 1972-03-16 1975-05-26 Thomae Gmbh Dr K Verfahren zur herstellung von neuen optisch aktiven 1-(4'-amino-3'-halogenphenyl)-2-aminoäthanolen und deren säureadditionssalzen
DD124521A1 (fr) 1976-03-16 1977-03-02
US6022637A (en) 1984-10-23 2000-02-08 Wilson; John T. R. High temperature battery
JPH0690934B2 (ja) 1987-08-07 1994-11-14 日本電信電話株式会社 二次電池およびその製造方法
SG42938A1 (en) 1993-02-26 1997-10-17 Ciba Geigy Ag Ferrocenc diphosphines as ligands for homogeneous catalysts
DE59408655D1 (de) 1993-10-01 1999-09-30 Novartis Ag Mit Fluoralkyl substituierte Ferrocenyldiphosphine als Liganden für homogene Katalysatoren
JPH07326372A (ja) 1994-05-30 1995-12-12 Yuasa Corp 固体電解質電池
DE4426245A1 (de) 1994-07-23 1996-02-22 Gruenenthal Gmbh 1-Phenyl-3-dimethylamino-propanverbindungen mit pharmakologischer Wirkung
EP0729969B1 (fr) 1995-02-24 2000-08-16 Novartis AG Ligandes ferrocène-disphosphine silylée, support inorganique ou à base de polymères organiques les contenant et leurs complexes métalliques et procédé de préparation et utilisation
EP0728768B1 (fr) 1995-02-24 2002-08-28 Syngenta Participations AG Polymères renfermant des groupements diphosphines dans les chaínes latérales et leurs complexes métalliques
US6337156B1 (en) 1997-12-23 2002-01-08 Sri International Ion battery using high aspect ratio electrodes
JPH11345629A (ja) 1998-03-31 1999-12-14 Canon Inc 二次電池及びその製造方法
DE19933421A1 (de) * 1999-07-16 2001-01-25 Gruenenthal Gmbh 2-Benzyl-3-dimethylamino-1-phenyl-propanderi- vate
DE10000311A1 (de) 2000-01-05 2001-07-12 Gruenenthal Gmbh Aminomethyl-Phonyl-Cyclohexanonderivate
JP4951809B2 (ja) 2000-11-21 2012-06-13 日油株式会社 二次電池用電解質および二次電池
JP4777593B2 (ja) 2002-11-29 2011-09-21 株式会社オハラ リチウムイオン二次電池の製造方法
JP4366101B2 (ja) 2003-03-31 2009-11-18 キヤノン株式会社 リチウム二次電池
CN1768046A (zh) 2003-04-07 2006-05-03 索尔维亚斯股份公司 胺取代的二苯基二膦及其在用于不对称合成的金属配合物中的应用
DE10326097A1 (de) 2003-06-06 2005-01-05 Grünenthal GmbH Verfahren zur Herstellung von Dimethyl-(3-aryl-butyl)-aminverbindungen
DE10328316A1 (de) 2003-06-23 2005-01-20 Grünenthal GmbH Verfahren zur Herstellung von Dimethyl-(3-aryl-buthyl)-aminverbindungen als pharmazeutische Wirkstoffe
KR101057284B1 (ko) 2005-10-26 2011-08-16 일라이 릴리 앤드 캄파니 선택적 ｖｐａｃ２ 수용체 펩티드 작동제

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4012456A (en) * 1974-11-19 1977-03-15 Chaplits Donat N Method for separation of isobutylene from C4 hydrocarbon fractions
US4276195A (en) * 1979-12-20 1981-06-30 Iowa State University Research Foundation, Inc. Converting homogeneous to heterogeneous catalysts
US5811582A (en) * 1996-03-13 1998-09-22 Gruenenthal Gmbh Dimethyl-(3-aryl-but-3-enyl)-amine compounds as pharmaceutical active ingredients

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8704002B2 (en) 2003-06-23 2014-04-22 Grünenthal GmbH Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis
US20090043132A1 (en) * 2005-11-02 2009-02-12 Gruenenthal Gmbh Process for Preparing a Substituted Dimethyl-(3-arylbutyl)amine Compound by Homogeneous Catalysis
US8791300B2 (en) 2005-11-02 2014-07-29 Gruenenthal Gmbh Process for preparing a substituted dimethyl-(3-arylbutyl)amine compound by homogeneous catalysis
US8138376B2 (en) * 2006-07-24 2012-03-20 Janssen Pharmaceutica, Nv Preparation of (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentanamine
US8877974B2 (en) 2006-07-24 2014-11-04 Grünenthal GmbH Process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropy1)-phenol
US20100099916A1 (en) * 2006-07-24 2010-04-22 Gruenenthal Gmbh Process for the Preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol
US8263809B2 (en) 2006-07-24 2012-09-11 Gruenenthal Gmbh Preparation of 3-[(1R,2R)-3-(dimethylamino)-1ethyl-2-methylpropyl]phenol
US11739049B2 (en) 2006-07-24 2023-08-29 Grünenthal GmbH Process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol
US20090326271A1 (en) * 2006-07-24 2009-12-31 Gruenenthal Gmbh Preparation of 3-[(1R,2R)-3-(Dimethylamino)-1Ethyl-2-Methylpropyl]phenol
US20090312578A1 (en) * 2006-07-24 2009-12-17 Filliers Walter Ferdinand Mari Preparation of (2r,3r)-3-(3-methoxyphenyl)-n,n,2-trimethylpentanamine
US20110071120A1 (en) * 2009-09-22 2011-03-24 Actavis Group Ptc Ehf Solid state forms of tapentadol salts
US9512060B2 (en) 2009-09-22 2016-12-06 Actavis Group Ptc Ehf Solid state forms of tapentadol salts
US8288592B2 (en) 2009-09-22 2012-10-16 Actavis Group Ptc Ehf Solid state forms of tapentadol salts
US8981154B2 (en) 2009-09-22 2015-03-17 Actavis Group Ptc Ehf Solid state forms of tapentadol salts
CN103168025A (zh) * 2010-06-15 2013-06-19 格吕伦塔尔有限公司 用于制备取代的3-(1-氨基-2-甲基戊烷-3-基)苯基化合物的方法
US9388119B2 (en) 2010-06-15 2016-07-12 Gruenenthal Gmbh Process for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds
US8669399B2 (en) 2010-06-15 2014-03-11 Grünenthal GmbH Process for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds
EP2666765A3 (fr) * 2010-06-15 2013-12-11 Grünenthal GmbH Procédé de préparation de composés de 3-(1-amino-2-méthylpentane-3-yl)phényl substitués
US9850198B2 (en) 2010-06-15 2017-12-26 Gruenenthal Gmbh Process for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds
EP2792668A1 (fr) * 2010-06-15 2014-10-22 Grünenthal GmbH Procédé de préparation de composés de 3-(1-amino-2-méthylpentane-3-yl)phényl substitués
WO2011157390A3 (fr) * 2010-06-15 2012-03-15 Grünenthal GmbH Procédé de préparation de composés 3-(1-amino-2-methylpentane-3-yl)phényle substitué
WO2012038974A1 (fr) 2010-09-20 2012-03-29 Ind-Swift Laboratories Limited Procédé de préparation de dérivés de l-phényl-3-diméthylaminopropane
US8552219B2 (en) 2010-09-20 2013-10-08 Ind-Swift Laboratories Limited Process for preparing L-phenyl-3-dimethylaminopropane derivative
WO2013105109A1 (fr) * 2011-11-09 2013-07-18 Indoco Remedies Limited Procédé de préparation de tapentadol
WO2013185928A1 (fr) 2012-06-15 2013-12-19 Siegfried Ag Procédé de préparation de composés 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane
EP2674414A1 (fr) 2012-06-15 2013-12-18 Siegfried AG Appareils dýimpression
US9090539B2 (en) 2013-05-24 2015-07-28 Ampac Fine Chemicals Llc Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds
WO2015075678A1 (fr) 2013-11-21 2015-05-28 Unimark Remedies Ltd. Nouveau procédé pour la préparation de dérivés de 1-phényl-3-aminopropane
US9914695B2 (en) 2015-07-10 2018-03-13 Mallinckrodt Llc Two-step process for preparing 3-substituted phenylalkylamines

Also Published As

Publication number Publication date
EP1636169B1 (fr) 2010-06-02
CN101774932A (zh) 2010-07-14
IL172692A0 (en) 2006-04-10
DE10328316A1 (de) 2005-01-20
US8704002B2 (en) 2014-04-22
ATE469877T1 (de) 2010-06-15
ES2345658T3 (es) 2010-09-29
DE502004011239D1 (de) 2010-07-15
IL172692A (en) 2011-03-31
PL1636169T3 (pl) 2010-11-30
US20130060065A1 (en) 2013-03-07
WO2005000788A1 (fr) 2005-01-06
CN1809527A (zh) 2006-07-26
CN1809527B (zh) 2010-05-26
PT1636169E (pt) 2010-07-21
SI1636169T1 (sl) 2010-09-30
CN101774932B (zh) 2013-10-30
HK1088598A1 (en) 2006-11-10
EP1636169A1 (fr) 2006-03-22

Similar Documents

Publication Publication Date Title
US8704002B2 (en) Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis
US11739049B2 (en) Process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol
ZA200204066B (en) Process of preparing tolterodine and analogues thereof as well as intermediates prepared in the process.
HK1088598B (en) Method for dehydrating substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and method for producing substituted dimethyl-(3-aryl-butyl)-amine compounds by means of heterogeneous catalysis
HK1162463B (en) Process for the preparation of (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol
HK1162463A (en) Process for the preparation of (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol
HK1130246B (en) Process for the preparation of (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol
HK1243056B (en) Process for the preparation of (1r,2r)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol

Legal Events

Date Code Title Description
AS Assignment

Owner name: GRUENENTHAL GMBH, GERMANY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JAGUSCH, UTZ-PETER;HOELDERICH, WOLFGANG;WISSLER, MONIKA;REEL/FRAME:017756/0731;SIGNING DATES FROM 20060304 TO 20060320

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO PAY ISSUE FEE