US2006167318A1PendingUtilityA1
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
Est. expiryJun 23, 2023(expired)· nominal 20-yr term from priority
C07B 2200/07C07C 213/08
57
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Claims
Abstract
Process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds. The process comprises dehydration by heterogeneous catalysis of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds, to form substituted dimethyl-(3-aryl-but-3-enyl)-amine intermediates, which are then converted by hydrogenation with hydrogen to substituted dimethyl-(3-aryl-butyl)-amine compounds.
Claims
exact text as granted — not AI-modified1 . A method for converting a one compound of Formula I
wherein
R 1 represents H or C 1-5 -alkyl,
R 1′ represents H or C 1-5 -alkyl,
R 2 represents H or C 1-5 -alkyl,
R 3 represents H or C 1-5 -alkyl,
R 4 , R 4′ , R 5 , R 5′ , R 6 , which may be identical or different, each represents H, OH, C 1-4 -alkyl, OC 1-4 -alkyl, partially fluorinated or perfluorinated C 1-4 -alkyl, partially fluorinated or perfluorinated O—C 1-4 -alkyl, O—(CH 2 ) n -phenyl where n=1, 2 or 3, F, C 1 or OR 8 ,
or two adjacent radicals R 4 and R 5 , R 5 and R 6 , R 6 and R 5′ or R 5′ and R 4′ represent a group —OCH═CHO—, —CH═C(R 9 )—O—, —CH═C(R 9 )—S— or —CH═CH—C(OR 10 )═CH— as part of a ring, with the proviso that the other radicals in each case R 6 , R 5′ and R 4′ ; R 4 , R 5′ and R 6′ ; R 4 , R 5 and R 4′ or R 4 , R 5 and R 6 are as defined above,
R 8 represents CO-C 1-5 -alkyl, PO(O-C 1-4 -alkyl) 2 , CO—C 6 H 4 —R 11 , CO(O-C 1-5 -alkyl), CO—CHR 12 —NHR 13 , CO—NH—C 6 H 3 —(R 14 ) 2 or an unsubstituted or substituted pyridyl, thienyl, thiazoyl or phenyl group,
R 9 represents H or C 1-4 -alkyl,
R 10 represents H or C 1-3 -alkyl,
R 11 represents OC(O)-C 1-3 -alkyl in the ortho-position or —CH 2 —N—(R 15 ) 2 in the meta- or para-position, where R 15 in each case represents C 1-4 -alkyl or the two radicals R 15 , together with the bridging nitrogen atom, form a 4-morpholino radical,
R 12 and R 13 , which may be identical or different, each represents H, C 1-6 -alkyl or C 3-8 -cycloalkyl,
or R 12 and R 13 together represent —(CH 2 ) 3-8 as part of a ring,
R 14 represents H, OH, C 1-7 -alkyl, partially fluorinated or perfluorinated C 1-7 -alkyl, OC 1-7 -alkyl, phenyl, O-aryl, F or Cl, with the proviso that the radicals R 14 are identical or different,
wherein in each case the compound of Formula I is in the form of one of its pure stereoisomers, a racemate, or in the form of a mixture of stereoisomers, 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,
wherein the method comprises dehydrating the compound of Formula I via heterogeneous catalysis to form a compound of Formula II
wherein 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 its pure stereoisomers, a racemate, or a mixture of stereoisomers, 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.
2 . The method according to Clam 1 , wherein the stereoisomer of a compound of Formula I or Formula II is an enantiomer or a diastereoisomer.
3 . A method for the preparation of a compound of Formula III
wherein a compound of Formula I is dehydrated with heterogeneous catalysis according to claim 1 to form a compound of Formula II as an intermediate,
wherein R 1 , R 1′ , R 2 , R 3 , R 4 , R 4′ , R 5 , R 5′ and R 6 are as defined in claim 1 , and wherein the intermediate is reacted to form a compound of Formula III as end product.
4 . The method according to claim 3 , wherein the intermediate is isolated or purified.
5 . The method according to claim 3 , wherein the intermediate is converted to the end product via heterogeneous catalysis.
6 . The method according to claim 4 , wherein the intermediate is converted to the end product by hydrogenation with hydrogen.
7 . The method according to claim 1 , wherein the compound of Formula I is converted to Formula II in the presence of at least one acidic catalyst, or at least one basic catalyst.
8 . The method according to claim 7 , wherein the compound of Formula I is converted to Formula II in the presence of at least one acidic catalyst.
9 . The method according to claim 8 , wherein the acidic catalyst is selected from the group consisting of ion-exchange resins, zeolites, heteropoly comprises a component acids, phosphates, and sulfates.
10 . The method according to claim 8 , wherein the acidic catalyst comprises at least one metal oxide mixed with a component selected from the group consisting of ion-exchange resins, zeolites, heteropoly acids, phosphates, and sulfates.
11 . The method according to claim 9 , wherein the ion-exchange resin contains sulfonic acid groups.
12 . The method according to claim 10 , wherein the ion-exchange resin contains sulfonic acid groups.
13 . The method according to claim 9 , wherein the ion-exchange resin is based on at least one tetrafluoroethylene/perfluorovinyl ether copolymer.
14 . The method according to claim 10 , wherein the ion-exchange resin is based on at least one tetrafluoroethylene/perfluorovinyl ether copolymer.
15 . The method according to claim 9 , wherein the ion-exchange resin is based on at least one styrene/divinylbenzene copolymer.
16 . The method according to claim 10 , wherein the ion-exchange resin is based on at least one styrene/divinylbenzene copolymer.
17 . The method according to claim 10 , wherein the at least one metal oxide is selected from the group consisting of SiO 2 , Al 2 O 3 , TiO 2 , Nb 2 O 5 , B 2 O 3 , a mixture of Nb 2 O 5 and B 2 O 3 , a mixture of Al 2 O 3 and SiO 2 , and a mixture of Al 2 O 3 and B 2 O 3 .
18 . The method according claim 3 , wherein the reaction to form the compound of Formula III is carried out in the presence of at least one catalyst that comprises one or more transition metal.
19 . The method according to claim 18 , wherein the reaction is carried out further in the presence of at least one acidic or basic catalyst.
20 . The method according claim 3 , wherein the reaction to form the compound of Formula III is carried out in the presence of at least one polyfunctionalized catalyst.
21 . The method according claim 20 , wherein the polyfunctionalized catalyst is a bifunctionalized catalyst.
22 . The method according to claim 21 , wherein the bifunctionalized catalyst is an acidic or basic catalyst.
23 . The method according to claim 22 , wherein the bifunctionalized catalyst comprises one or more transition metals.
24 . The method according to claim 23 , wherein the bifunctionalized catalyst is acidic and comprises one or more transition metals.
25 . The method according to claim 3 , wherein the dehydration step to form the intermediate is carried out without purification or isolation.
26 . The method according to claim 25 , wherein both the dehydration step to form the intermediate and the reaction to form the end product are carried out without purification or isolation.
27 . The method according to claim 26 , wherein to reaction to form the end product is carried out in the presence of at least one polyfunctionalized catalyst.
28 . The method according claim 27 , wherein the polyfunctionalized catalyst is a bifunctionalized catalyst.
29 . The method according to claim 28 , wherein the bifunctionalized catalyst is an acidic or basic catalyst.
30 . The method according to claim 29 , wherein the bifunctionalized catalyst comprises one or more transition metals.
31 . The method according to claim 30 , wherein the bifunctionalized catalyst is acidic and comprises one or more transition metals.
32 . The method according to claim 27 , wherein the catalyst comprises at least one ion-exchange resin that comprises one or more transition metals.
33 . The method according to claim 32 , wherein the ion-exchange resin comprises sulfonic acid groups.
34 . The method according to claim 33 , wherein the ion-exchange resin is based on at least one tetrafluoroethylene/perfluorovinyl ether copolymer.
35 . The method according to claim 33 , wherein the ion-exchange resin is based on at least one styrene/divinylbenzene copolymer.
36 . The method according to claim 31 , wherein the at least one transition metal is 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.
37 . The method according to claim 36 , wherein the at least one transition metal is selected from the group consisting of Ru, Rh, Pd, Os, Ir and Pt.
38 . The method according to claim 37 , wherein the at least one transition metal is selected from the group consisting of Pd, Ru, Pt and Ir.
39 . The method according to claim 38 , wherein the transition metal is Pd.
40 . The method according to claim 31 , wherein the at least one transition metal is present in the same or different oxidation states.
41 . The method according to claim 40 , wherein the transition metal is present in at least two different oxidation states.
42 . A method for preparing a compound of Formula III
wherein
R 1 represents H or C 1-5 -alkyl,
R 1′ represents H or C 1-5 -alkyl,
R 2 represents H or C 1-5 -alkyl,
R 3 represents H or C 1-5 -alkyl,
R 4 , R 4′ , R 5 , R 5′ , R 6 , which may be identical or different, each represents H, OH, C 1-4 -alkyl, OC 1-4 -alkyl, partially fluorinated or perfluorinated C 1-4 -alkyl, partially fluorinated or perfluorinated O—C 1-4 -alkyl, O—(CH 2 ) n -phenyl where n=1, 2 or 3, F, Cl or OR 8 ,
or two adjacent radicals R 4 and R 5 , R 5 and R 6 , R 6 and R 5′ or R 5′ and R 4′ represent a group —OCH═CHO—, —CH═C(R 9 )—O—, —CH═C(R 9 )—S— or —CH═CH—C(OR 10 )═CH— as part of a ring, with the proviso that the other radicals in each case R 6 , R 5′ and R 4′ ; R 4 , R 5 and R 6′ ; R 4 , R 5 and R 4′ or R 4 , R 5 and R 6 are as defined above,
R 8 represents CO-C 1-5 -alkyl, PO(O-C 1-4 -alkyl) 2 , CO—C 6 H 4 —R 11 , CO(O-C 1-5 -alkyl), CO—CHR 12 —NHR 13 , CO—NH—C 6 H 3 —(R 14 ) 2 or an unsubstituted or substituted pyridyl, thienyl, thiazoyl or phenyl group,
R 9 represents H or C 1-4 -alkyl,
R 10 represents H or C 1-3 -alkyl,
R 11 represents OC(O)-C 1-3 -alkyl in the ortho-position or —CH 2 —N—(R 15 ) 2 in the meta- or para-position, where R 15 in each case represents C 1-4 -alkyl or the two radicals R 15 , together with the bridging nitrogen atom, form a 4-morpholino radical,
R 12 and R 13 , which may be identical or different, each represents H, C 1-6 -alkyl or C 3-8 -cycloalkyl,
or R 12 and R 13 together represent —(CH 2 ) 3-8 as part of a ring,
R 14 represents H, OH, C 1-7 -alkyl, partially fluorinated or perfluorinated C 1-7 -alkyl, OC 1-7 -alkyl, phenyl, O-aryl, F or Cl, with the proviso that the radicals R 14 are identical or different,
wherein in each case the compound of Formula III is in the form of one of its pure stereoisomers, a racemate, or in the form of a mixture of stereoisomers 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,
the method comprising reacting a compound of Formula II
wherein 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, of their racemates or in the form of a mixture of stereoisomers 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,
via hydrogenation with hydrogen by way of heterogeneous catalysis in the presence of a mixture comprising at least one acidic catalyst or one basic catalyst and at least one catalyst containing one or more transition metals, or in the presence of at least one bifunctionalized catalyst which is acidic or basic and contains one or more transition metals.
43 . The method according to claim 42 , wherein the mixture comprises an acidic catalyst.
44 . The method according to claim 42 , wherein the bifunctionalized catalyst is acidic.
45 . The method according to claim 42 , wherein the at least one transition metal is 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.
46 . The method according to claim 45 , wherein the at least one transition metal is selected from the group consisting of Ru, Rh, Pd, Os, Ir and Pt.
47 . The method according to claim 46 , wherein the at least one transition metal is selected from the group consisting of Pd, Ru, Pt and Ir.
48 . The method according to claim 47 , wherein the transition metal is Pd.
49 . The method according to claim 42 , wherein the at least one transition metal is present in the same or different oxidation states.
50 . The method according to claim 40 , wherein the transition metal is present in at least two different oxidation states.
51 . The method according to claim 3 , wherein the compound of Formula I or the compound of Formula II is mixed with or dissolved in a reaction medium that is liquid under reaction conditions.
52 . The method according to claim 51 , wherein the compound of Formula I and the compound of Formula II are mixed with or dissolved in a reaction medium that is liquid under reaction conditions.
53 . The method according to claim 51 , wherein the reaction medium is based on water, on one or more organic compounds, or on a mixture of water and one or more organic compounds.
54 . The method according to claim 53 , wherein the organic compound is selected from the group consisting of halogenated organic compounds, alcohols and ketones.
55 . The method according to claim 54 , wherein the organic compound is selected from the group consisting of dichloromethane, chloroform, toluene, methanol, ethanol, and acetone.
56 . The method according to claim 55 , wherein the organic compound is methanol or ethanol or a mixture thereof.
57 . The method according to claim 42 , wherein the compound of Formula I or the compound of Formula II is mixed with or dissolved in a reaction medium that is liquid under reaction conditions.
58 . The method according to claim 57 , wherein the compound of Formula I and the compound of Formula II are mixed with or dissolved in a reaction medium that is liquid under reaction conditions.
59 . The method according to claim 58 , wherein the reaction medium is based on water, on one or more organic compounds or on a mixture of water and one or more organic compounds.
60 . The method according to claim 59 , wherein the organic compound is selected from the group consisting of halogenated organic compounds, alcohols and ketones.
61 . The method according to claim 60 , wherein the organic compound is selected from the group consisting of dichloromethane, chloroform, toluene, methanol, ethanol, and acetone.
62 . The method according to claim 61 , wherein the organic compound is methanol or ethanol or a mixture thereof.
63 . The method according to claim 3 , wherein the dehydration to form the intermediate or the reaction to form the end product is each carried out at temperatures ranging from about 20 to about 250° C.
64 . The method according to claim 63 , wherein the dehydration to form the intermediate and the reaction to form the end product are each carried out at temperatures ranging from about 20 to about 250° C.
65 . The method according to claim 64 , wherein the reaction is carried out at a temperature ranging from about 50 to about 180° C.
66 . The method according to claim 65 , wherein the reaction is carried out at a temperature ranging from about 100 to about 160° C.
67 . The method according to claim 43 , wherein the dehydration to form the intermediate or the reaction to form the end product is each carried out at temperatures ranging from about 20 to about 250° C.
68 . The method according to claim 67 , wherein the dehydration to form the intermediate and the reaction to form the end product are each carried out at temperatures ranging from about 20 to about 250° C.
69 . The method according to claim 68 , wherein the reaction is carried out at a temperature ranging from about 50 to about 180° C.
70 . The method according to claim 69 , wherein the reaction is carried out at a temperature ranging from about 100 to about 160° C.
71 . The method according to claim 3 , wherein the dehydration to form the intermediate or the reaction to form the end product is each carried out at a pressure of from about 0.01 to about 300 bar.
72 . The method according to claim 71 , wherein the dehydration to form the intermediate and the reaction to form the end product are each carried out at a pressure of from about 2 to about 10 bar.
73 . The method according to claim 42 , wherein the dehydration to form the intermediate or the reaction to form the end product is each carried out at a pressure of from about 0.01 to about 300 bar.
74 . The method according to claim 73 , wherein the dehydration to form the intermediate and the reaction to form the end product are each carried out at a pressure of from about 2 to about 10 bar.
75 . The method according to claim 3 , wherein the dehydration to form the intermediate or the reaction to form the end product is each carried out discontinuously.
76 . The method according to claim 75 , wherein the dehydration to form the intermediate and the reaction to form the end product are each carried out in a slurry reactor.
77 . The method according to claim 42 , wherein the dehydration to form the intermediate or the reaction to form the end product is each carried out discontinuously.
78 . The method according to claim 77 , wherein the dehydration to form the intermediate and the reaction to form the end product are each carried out in a slurry reactor.Join the waitlist — get patent alerts
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