CA2484685A1 - Optically active .beta.-aminoketones, optically active 1,3-amino alcohols and method for the production thereof - Google Patents
Optically active .beta.-aminoketones, optically active 1,3-amino alcohols and method for the production thereof Download PDFInfo
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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Abstract
The invention relates to chiral Mannich bases of formula (I),chiral 1.3 aminoalcohols of formula (II) derived therefrom and a method for the production of (I) and (II), beginning with Mannich salts of formula (III) containing a chiral anion Y*-.
Claims (30)
1. A compound of the formula (I) or its enantiomer, where R1 is 1. hydrogen,
2. a tert-butyl group or
3. a carbocyclic or heterocyclic aryl radical R6, where the aryl radical R6 is a carbocyclic aryl radical having 5-14 carbon atoms or a heterocyclic aryl radical having 5-14 carbon atoms, where from 1 to 4 carbon atoms are replaced by N, O or S, where R6 is unsubstituted or bears from 1 to 5 substituents which are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl, alkanoyl (-CO-(C1-C7)alkyl), aroyl (-CO-(C5-C14)aryl), fluoro, chloro, bromo, iodo, hydroxyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, -O-CO-SR, -O-CS-NHR, -O-CS-NRR', -O-CS-OR, -O-CS-SR, -O-SO2-(C1-C7)alkyl, -O-SO2-(C5-C14)aryl, nitro, -NH-CO-R, -NR'-CO-R, -NH-CO-OR, -NR'-CO-OR, -NH-CO-NHR, -NR'-CO-NHR, -NR'-CO-NRR", di(C1-C7)alkylamino, di(C5-C14)arylamino, N-(C1-C7)alkyl-N-(C5-C14)arylamino, (C1-C7)alkylthio, (C5-C14)arylthio, (C1-C7)alkylsulfonyl, (C5-C14)arylsulfonyl, (C5-C14)arylsulfoxidyl, or an unsubstituted aryl radical R6, where R, R' and R" are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl or (C5-C14)aryl, R2 , R3 and R4 are each independently 1. hydrogen, 2. (C1-C7)alkyl, where (C1-C7)alkyl is unsubstituted or substituted by an aryl radical R6, 3. (C3-C7)cycloalkyl or
4. an aryl radical R6, and R5 is an aryl radical R6.
2. A compound of the formula (I) as claimed in claim 1, where R6 is a carbocyclic aryl radical having 6-10 carbon atoms or a heterocyclic aryl radical having 6-carbon atoms; where from 1 to 4 carbon atoms are replaced by N, O or S.
3. A compound of the formula (I) as claimed in one of claims 1 and 2, where R6 is a radical from the group of phenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, quinolinyl, isoquinolinyl, benzoquinolinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, benzopyridazinyl, benzopyrimidinyl, benzopyrazinyl (quinoxalinyl), benzotriazinyl, pyridopyridinyl, pyridoquinolinyl (phenanthrolinyl), benzoquinoxalinyl (phenazinyl), pyrrolyl, benzopyrrolyl (indolyl), benzoindolyl, pyrazolyl, benzopyrazolyl, imidazolyl, benzimidazolyl, triazolyl, benzotriazolyl, tetrazolyl; imidazopyrimidinyl (9H-purinyl), furanyl, benzofuranyl, dibenzofuranyl, thiophene, benzothiophene, dibenzothiophene, isoxazolyl, benzisoxazolyl, oxazolyl, benzoxazolyl, oxadiazolyl, benzoxadiazolyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, thiadiazolyl or benzothiadiazolyl, where R6 is unsubstituted or provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl.
4. A compound of the formula (I) as claimed in one of claims 1 to 3, where R6 is a radical R' which is defined as a radical from the group of phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl, where R' is unsubstituted or is provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, benzoquinolinyl.
2. A compound of the formula (I) as claimed in claim 1, where R6 is a carbocyclic aryl radical having 6-10 carbon atoms or a heterocyclic aryl radical having 6-carbon atoms; where from 1 to 4 carbon atoms are replaced by N, O or S.
3. A compound of the formula (I) as claimed in one of claims 1 and 2, where R6 is a radical from the group of phenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, quinolinyl, isoquinolinyl, benzoquinolinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, benzopyridazinyl, benzopyrimidinyl, benzopyrazinyl (quinoxalinyl), benzotriazinyl, pyridopyridinyl, pyridoquinolinyl (phenanthrolinyl), benzoquinoxalinyl (phenazinyl), pyrrolyl, benzopyrrolyl (indolyl), benzoindolyl, pyrazolyl, benzopyrazolyl, imidazolyl, benzimidazolyl, triazolyl, benzotriazolyl, tetrazolyl; imidazopyrimidinyl (9H-purinyl), furanyl, benzofuranyl, dibenzofuranyl, thiophene, benzothiophene, dibenzothiophene, isoxazolyl, benzisoxazolyl, oxazolyl, benzoxazolyl, oxadiazolyl, benzoxadiazolyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, thiadiazolyl or benzothiadiazolyl, where R6 is unsubstituted or provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl.
4. A compound of the formula (I) as claimed in one of claims 1 to 3, where R6 is a radical R' which is defined as a radical from the group of phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl, where R' is unsubstituted or is provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, benzoquinolinyl.
5. A compound of the formula (I) as claimed in one of claims 1 to 4, where R6 is a radical R8 which is defined as a radical from the group of phenyl, naphthyl, pyridyl or quinolinyl, and which is unsubstituted or provided with up to 5 substituents which are each independently: nitro, fluoro, chloro or bromo.
6. A compound of the formula (I) as claimed in one of claims 1 to 5, where R2, and R4 are each independently hydrogen or a radical R7.
7. A compound of the formula (I) as claimed in one of claims 1 to 6, where R2, and R4 are each independently hydrogen or an aryl radical R8.
8. A compound of the formula (I) as claimed in one of claims 1 to 7, where R5 is a radical R4, preferably a radical R8.
9. A compound of the formula (II), where R1 is 1. hydrogen, 2. a tert-butyl group or 3. a carbocyclic or heterocyclic aryl radical R6, where the aryl radical R6 is a carbocyclic aryl radical having 5-14 carbon atoms or a heterocyclic aryl radical having 5-14 carbon atoms, where from 1 to 4 carbon atoms are replaced by N, O or S, where R6 is unsubstituted or bears from 1 to 5 substituents which are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl, alkanoyl (-CO-(C1-C7)alkyl), aroyl (-CO-(C5-C14)aryl), fluoro, chloro, bromo, iodo, hydroxyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, -O-CO-SR, -O-CS-NHR, -O-CS-NRR', -O-CS-OR, -O-CS-SR, -O-SO2-(C1-C7)alkyl, -O-SO2-(C5-C14)aryl, nitro, -NH-CO-R, -NR'-CO-R, -NH-CO-OR, -NR'-CO-OR, -NH-CO-NHR, -NR'-CO-NHR, -NR'-CO-NRR", di(C1-C7)alkylamino, di(C5-C14)arylamino, N-(C1-C7)alkyl-N-(C5-C14)arylamino, (C1-C7)alkylthio, (C5-C14)arylthio, (C1-C7)alkylsulfonyl, (C5-C14)arylsulfonyl, (C5-C14)arylsulfoxidyl, or an unsubstituted aryl radical R6, where R, R' and R" are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl or (C5-C14)aryl, R2, R3 and R4 are each independently 1. hydrogen, 2. (C1-C7)alkyl, where (C1-C7)alkyl is unsubstituted or substituted by an aryl radical R6, 3. (C3-C7)cycloalkyl or 4. an aryl radical R6, and R5 is an aryl radical R6, with the exception of a compound of the formula (II) where R1 = o-aminophenyl, R2 = H, R3 = 2-pyridyl, R4 = 2-pyridyl and R5 = phenyl or 3,5-dimethylisoxazol-4-yl, or an enantiomer of the compound of the formula (II) or a salt of the compound of the formula (II) or of an enantiomer of the compound of the formula (II).
10. A compound of the formula (II) as claimed in claim 9, where R6 is a carbocyclic aryl radical having 6-10 carbon atoms or a heterocyclic aryl radical having 6-carbon atoms, where from 1 to 4 carbon atoms ace replaced by N, O or S.
11. A compound of the formula (II) as claimed in one of claims 9 and 10, where R6 is a radical from the group of phenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, quinolinyl, isoquinolinyl, benzoquinolinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, benzopyridazinyl, benzopyrimidinyl, benzopyrazinyl (quinoxalinyl), benzotriazinyl, pyridopyridinyl, pyridoquinolinyl (phenanthrolinyl), benzoquinoxalinyl (phenazinyl), pyrrolyl, benzopyrrolyl (indolyl), benzoindolyl, pyrazolyl, benzopyrazolyl, imidazolyl, benzimidazolyl, triazolyl, benzotriazolyl, tetrazolyl, imidazopyrimidinyl (9H-purinyl), furanyl, benzofuranyl, dibenzofuranyl, thiophene, benzothiophene, dibenzothiophene, isoxazolyl, benzisoxazolyl, oxazolyl, benzoxazolyl, oxadiazolyl, benzoxadiazolyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, thiadiazolyl or benzothiadiazolyl;
where R6 is unsubstituted or provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl.
where R6 is unsubstituted or provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl.
12. A compound of the formula (II) as claimed in one of claims 9 to 11, where R6 is a radical R7 which is defined as a radical from the group of phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl or benzoquinolinyl, where R6 is unsubstituted or is provided with up to 5 substituents which are each independently: (C1-C7)alkyl, (C3-C7)cycloalkyl, fluoro, chloro, bromo, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, nitro, phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, benzoquinolinyl.
13. A compound of the formula (II) as claimed in one of claims 9 to 12, where R6 is a radical R8 which is defined as a radical from the group of phenyl, naphthyl, pyridyl or quinolinyl, and which is unsubstituted or provided with up to 5 substituents which are each independently: nitro, fluoro, chloro or bromo.
14.~A compound of the formula (II) as claimed in one of claims 9 to 13, where R2, R3 and R4 are each independently hydrogen or a radical R7.
15.~A compound of the formula (II) as claimed in one of claims 9 to 14, where R2, R3 and R4 are each independently hydrogen or an aryl radical R8.
16.~A compound of the formula (II) as claimed in one of claims 9 to 15, where R5 is a radical R7, preferably a radical R8.
17.~A process for preparing a compound of the formula (III) or its diastereomer where R1 is 1. hydrogen, 2. a tert-butyl group or 3. a carbocyclic or heterocyclic aryl radical R6, where the aryl radical R6 is a carbocyclic aryl radical having 5-14 carbon atoms or a heterocyclic aryl radical having 5-14 carbon atoms, where from 1 to 4 carbon atoms are replaced by N, O or S, where R6 is unsubstituted or bears from 1 to 5 substituents which are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl, alkanoyl (-CO-(C1-C7)alkyl), aroyl (-CO-(C5-C14)aryl), fluoro, chloro, bromo, iodo, hydroxyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, -O-CO-SR, -O-CS-NHR, -O-CS-NRR', -O-CS-OR, -O-CS-SR, -O-SO2-(C1-C7)alkyl, -O-SO2-(C5-C14)aryl, nitro, -NH-CO-R, -NR'-CO-R, -NH-CO-OR, -NR'-CO-OR, -NH-CO-NHR, -NR'-CO-NHR, -NR'-CO-NRR", di(C1-C7)alkylamino, di(C5-C14)arylamino, N-(C1-C7)alkyl-N-(C5-C14)arylamino, (C1-C7)alkylthio, (C5-C14)arylthio, (C1-C7)alkylsulfonyl, (C5-C14)arylsulfonyl, (C5-C14)arylsulfoxidyl, or an unsubstituted aryl radical R6, where R, R' and R" are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl or (C5-C14)aryl, R2, R3 and R4 are each independently 1. hydrogen, 2. (C1-C7)alkyl, where (C1-C7)alkyl is unsubstituted or substituted by an aryl radical R6;
3. (C3-C7)cycloalkyl or 4. an aryl radical R6, and R5 is an aryl radical R6, and where the anion Y*- is the conjugated base of an optically active, organic Br~nsted acid (protic acid), which comprises converting the compounds of the formulae (IV), (V), (VI) and (VII) where the R1, R2, R3, R4 and R5 radicals in the compounds of the formulae (IV), (V), (VI) and (VII) are defined as above, in a suitable solvent to the compound of the formula (III), by either reacting the compounds of the formulae (IV), (V), (VI) and (VII) at the same time in a direct Mannich reaction, or initially reacting the compounds of the formulae (IV) and (V) to give an imine of the formula (X) or to an aminal of the formula (XI) which can optionally be isolated and then converting the compound of the formula (X) or (XI) with the addition of the compounds of the formula (VI) and (VII) to a compound of the formula (III).
3. (C3-C7)cycloalkyl or 4. an aryl radical R6, and R5 is an aryl radical R6, and where the anion Y*- is the conjugated base of an optically active, organic Br~nsted acid (protic acid), which comprises converting the compounds of the formulae (IV), (V), (VI) and (VII) where the R1, R2, R3, R4 and R5 radicals in the compounds of the formulae (IV), (V), (VI) and (VII) are defined as above, in a suitable solvent to the compound of the formula (III), by either reacting the compounds of the formulae (IV), (V), (VI) and (VII) at the same time in a direct Mannich reaction, or initially reacting the compounds of the formulae (IV) and (V) to give an imine of the formula (X) or to an aminal of the formula (XI) which can optionally be isolated and then converting the compound of the formula (X) or (XI) with the addition of the compounds of the formula (VI) and (VII) to a compound of the formula (III).
18. The process as claimed in claim 17, where Y*- is an optically active, naturally occurring or industrially prepared carboxylic acid, preferably from the group of (R)-(-)-mandelic acid, (S)-(+)-mandelic acid, D-(-)-tartaric acid, L-(+)-tartaric acid, (+)-di-O,O'-pivaloyl-D-tartaric acid [(+)-DPTA], (-)-di-O,O'-pivaloyl-L-tartaric acid, [(-)-DPTA], (+)-O,O'-dibenzoyl-D-tartaric acid, (-)-O,O'-dibenzoyl-L-tartaric acid, (-)-di-O,O'-benzoyl-L-tartaric mono(dimethylamide), (+)-O,O'-dianisoyl-D-tartaric acid [(+)-DATA], (-)-O,O'-dianisoyl-L-tartaric acid [(-)-DATA], (+)-di-O,O'-p-tolyl-D-tartaric acid, (-)di-O,O'-p-tolyl-L-tartaric acid, D-(+)-malic acid, L-(-)-malic acid, L-(+)-lactic acid, D-(-)-lactic acid, (S)-(-)-2-(phenylaminocarbonyloxy)propionic acid, (R)-(+)-2-(phenylaminocarbonyloxy)propionic acid, D-(+)-gluconic acid, (-)-2,3,4,6-di-O-isopropylidene-2-keto-L-gulonic acid, (D)-(-)-quinic acid, (-)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid [shikimic acid], (S)-(+)-(2,2-dimethyl-5-oxodioxolan-4-yl)acetic acid, (+)-camphoric acid, (-)-camphoric acid, (1R)-(+)-camphanic acid, (1S)(-)-camphanic acid, (R)-(-)-O-acetylmandelic acid, (S)-(+)-O-acetylmandelic acid, (R)-2-phenoxypropionic acid, (S)-2-phenoxypropionic acid, (S)-(+)-.alpha.-methoxyphenylacetic acid, (R)-(-)-.alpha.-methoxyphenylacetic acid, (R)-(+)-.alpha.-methoxy-.alpha.-trifluoromethylphenylacetic acid, (S)-(-)-.alpha.-methoxy-.alpha.-trifluoromethylphenylacetic acid, (S)-(+)-2-phenylpropionic acid, (R)-(-)-2-phenylpropionic acid, (R)-(+)2-chloropropionic acid, (S)-(-)-2-chloropropionic acid, (R)-(+)-N-(.alpha.-methylbenzyl)phthalic monoamide, (S)(-)-N-(.alpha.-methylbenzyl)phthalic monoamide, (R)-(-)-5-oxotetrahydrofuran-2-carboxylic acid, (S)-(+)-5-oxotetrahydrofuran-2-carboxylic acid, D-(+)-3-phenyllactic acid, L-(-)-3-phenyllactic acid, L-(+)-.alpha.-hydroxyisovaleric acid, D-(-)-.alpha.-hydroxyisovaleric acid, (+)-menthyloxyacetic acid, (-)-menthyloxyacetic acid, (+)-mono-(1S)-menthyl phthalate, (-)-mono-(1R)-menthyl phthalate, (+)-trans-5-norbornene-2,3-dicarboxylic acid, (-)-trans-5-norbornene-2,3-dicarboxylic acid, (R)-(+)-methylsuccinic acid, (S)(-)methylsuccinic acid, (R)-(+)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [(R)-(+)-Trolox ®], (S)-(-)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [(S)-(-)-Trolox ®], (S)-(+)-2-(4-isobutyl-phenyl)propionic acid [(S)-ibuprofen], (R)-(-)-2-(4-isobutylphenyl)propionic acid [(R)-ibuprofen], (+)-2-(6-methoxy-2-naphthyl)propionic acid [(+)-naproxen], (-)-2-(6-methoxy-2-naphthyl)propionic acid [(-)-naproxen], and also the available natural or unnatural .alpha.- or .beta.-amino acids and their readily accessible derivatives, in particular N-acylated derivatives, or an optically active sulfonic acid, preferably (1S)-(+)-camphor-10-sulfonic acid, (1R)-(-)-camphor-10-sulfonic acid, (-)-3-bromocamphor-8-sulfonic acid or (+)-3-bromocamphor-10-sulfonic acid, or an optically active phosphoric acid, phosphinic acid or phosphonic acid derivative, preferably (R)(-)-1,1'-binaphthalene-2,2'-diyl hydrogenphosphate, (S)-(+)-1,1'-binaphthalene-2,2'-diyl hydrogenphosphate, (+)-phosphinothricin or (-)-phosphinothricin, or an optically active phenol, preferably (R)-(+)- or (S)-(-)-binaphthol.
19. The process as claimed in one of claims 17 and 18, wherein the suitable solvent is water or an organic solvent, or a mixture of water with an organic solvent, optionally comprising a solubility-enhancing additive, where organic solvents may be present in 100% purity or technical quality, preferably a C1-C8-alcohol, branched or unbranched, more preferably methanol, ethanol, n-propanol, isopropanol or n-butanol, or a ketonic solvent, more preferably acetone or methyl ethyl ketone (MEK), or an ester, more preferably ethyl acetate or n-butyl acetate, or an ether, more preferably tetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, 1,2-dimethoxyethane or diethylene glycol dimethyl ether (diglyme), or a hydrocarbon, aliphatic or aromatic, more preferably toluene, or a supercritical medium, more preferably supercritical carbon dioxide or a halogenated hydrocarbon, more preferably dichloromethane, or a polar, aprotic solvent, more preferably DMF, DMSO or NMP.
20. The process as claimed in one of claims 17 to 19, wherein water present in the reaction is removed by azeotropic distillation or by adding water-binding additives, preferably magnesium sulfate or activated molecular sieves.
21. A process for preparing a compound of the formula (I) or its enantiomer ~
where R1 is 1. hydrogen, 2. a tert-butyl group or 3. a carbocyclic or heterocyclic aryl radical R6, where the aryl radical R6 is a carbocyclic aryl radical having 5-14 carbon atoms or a heterocyclic aryl radical having 5-14 carbon atoms, where from 1 to 4 carbon atoms are replaced by N, O or S, where R6 is unsubstituted or bears from 1 to 5 substituents which are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl, alkanoyl (-CO-(C1-C7)alkyl), aroyl (-CO-(C5-C14)aryl), fluoro, chloro, bromo, iodo, hydroxyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, -O-CO-SR, -O-CS-NHR, -O-CS-NRR', -O-CS-OR, -O-CS-SR, -O-SO2-(C1-C7)alkyl, -O-SO2-(C5-C14)aryl, nitro, -NH-CO-R, -NR'-CO-R, -NH-CO-OR, -NR'-CO-OR, -NH-CO-NHR, -NR'-CO-NHR, -NR'-CO-NRR", di(C1-C7)alkylamino, di(C5-C14)arylamino, N-(C1-C7)alkyl-N-(C5-C14)arylamino, (C1-C7)alkylthio, (C5-C14)arylthio, (C1-C7)alkylsulfonyl, (C5-C14)arylsulfonyl, (C5-C14)arylsulfoxidyl, or an unsubstituted aryl radical R6, where R, R' and R" are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl or (C5-C7a)aryl, R2, R3 and R4 are each independently 1. hydrogen, 2. (C1-C7)alkyl, where (C1-C7)alkyl is unsubstituted or substituted by an aryl radical R6, 3. (C3-C7)cycloalkyl or 4. an aryl radical R6, and R5 is an aryl radical R6, which comprises converting a compound of the formula (III) where the R1, R2, R3, R4 and R5 radicals are as defined above, by adding a suitable base in a suitable solvent.
where R1 is 1. hydrogen, 2. a tert-butyl group or 3. a carbocyclic or heterocyclic aryl radical R6, where the aryl radical R6 is a carbocyclic aryl radical having 5-14 carbon atoms or a heterocyclic aryl radical having 5-14 carbon atoms, where from 1 to 4 carbon atoms are replaced by N, O or S, where R6 is unsubstituted or bears from 1 to 5 substituents which are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl, alkanoyl (-CO-(C1-C7)alkyl), aroyl (-CO-(C5-C14)aryl), fluoro, chloro, bromo, iodo, hydroxyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, -O-CO-SR, -O-CS-NHR, -O-CS-NRR', -O-CS-OR, -O-CS-SR, -O-SO2-(C1-C7)alkyl, -O-SO2-(C5-C14)aryl, nitro, -NH-CO-R, -NR'-CO-R, -NH-CO-OR, -NR'-CO-OR, -NH-CO-NHR, -NR'-CO-NHR, -NR'-CO-NRR", di(C1-C7)alkylamino, di(C5-C14)arylamino, N-(C1-C7)alkyl-N-(C5-C14)arylamino, (C1-C7)alkylthio, (C5-C14)arylthio, (C1-C7)alkylsulfonyl, (C5-C14)arylsulfonyl, (C5-C14)arylsulfoxidyl, or an unsubstituted aryl radical R6, where R, R' and R" are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl or (C5-C7a)aryl, R2, R3 and R4 are each independently 1. hydrogen, 2. (C1-C7)alkyl, where (C1-C7)alkyl is unsubstituted or substituted by an aryl radical R6, 3. (C3-C7)cycloalkyl or 4. an aryl radical R6, and R5 is an aryl radical R6, which comprises converting a compound of the formula (III) where the R1, R2, R3, R4 and R5 radicals are as defined above, by adding a suitable base in a suitable solvent.
22. The process as claimed in claim 21, wherein a suitable base is an organic amine, preferably a (C1-C10)trialkylamine, more preferably a (C1-C3)trialkylamine, especially preferably triethylamine, diisopropylethylamine, or an alkali metal hydrogencarbonate, carbonate or hydroxide, or an alkaline earth metal hydrogencarbonate, carbonate or hydroxide, preferably sodium hydrogencarbonate or sodium hydroxide.
23. The process as claimed in claim 22, wherein a suitable solvent is water or an organic solvent, or a mixture of water with an organic solvent, optionally comprising a solubility-enhancing additive.
24. The process as claimed in one of claims 22 and 23, wherein the organic solvent is a C1-C8-alcohol, branched or unbranched, preferably methanol, ethanol, n-propanol, isopropanol or n-butanol, or a ketonic solvent, preferably acetone or methyl ethyl ketone (MEK), or an ester, preferably ethyl acetate or n-butyl acetate, or an ether, preferably tetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, 1,2-dimethoxyethane or diethylene glycol dimethyl ether (diglyme), or a hydrocarbon, aliphatic or aromatic, preferably toluene, or a supercritical medium, preferably supercritical carbon dioxide or a halogenated hydrocarbon, preferably dichloromethane, or a polar, aprotic solvent, preferably DMF, DMSO or NMP.
25. A process for preparing a compound of the formula (II) or its enantiomer, where R1 is 1. hydrogen, 2. a tert-butyl group or 3. a carbocyclic or heterocyclic aryl radical R6, where the aryl radical R6 is a carbocyclic aryl radical having 5-14 carbon atoms or a heterocyclic aryl radical having 5-14 carbon atoms, where from 1 to 4 carbon atoms are replaced by N, O or S, where R6 is unsubstituted or bears from 1 to 5 substituents which are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl, alkanoyl (-CO-(C1-C7)alkyl), aroyl (-CO-(C5-C14)aryl), fluoro, chloro, bromo, iodo, hydroxyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C5-C14)aryloxy, (C1-C7)alkanoyloxy, (C5-C14)aroyloxy, -O-CO-NHR, -O-CO-NRR', -O-CO-OR, -O-CO-SR, -O-CS-NHR, -O-CS-NRR', -O-CS-OR, -O-CS-SR, -O-SO2-(C1-C7)alkyl, -O-SO2(C5-C14)aryl, nitro, -NH-CO-R, -NR'-CO-R, -NH-CO-OR, -NR'-CO-OR, -NH-CO-NHR, -NR'-CO-NHR, -NR'-CO-NRR"; di(C1-C7)alkylamino, di(C5-C14)arylamino, N-(C1-C7)alkyl-N-(C5-C14)arylamino, (C1-C7)alkylthio, (C5-C14)arylthio, (C1-C7)alkylsulfonyl, (C5-C14)arylsulfonyl, (C5-C14)arylsulfoxidyl, or an unsubstituted aryl radical R6, where R, R' and R" are each independently (C1-C7)alkyl, (C3-C7)cycloalkyl or (C5-C14)aryl, R2 , R3 and R4 are each independently 1. hydrogen, 2. (C1-C7)alkyl, where (C1-C7)alkyl is unsubstituted or substituted by an aryl radical R6, 3. (C3-C7)cycloalkyl or 4. an aryl radical R6, and R5 is an aryl radical R6, which comprises reducing a compound of the formula (III) where the R1, R2, R3, R4 and R5 radicals are each as defined above, or a compound of the formula (I) with a suitable reducing agent, and then optionally working up and isolating.
26. The process as claimed in claim 25, wherein the reducing agent is a borane or borohydride reagent, optionally in the presence of a chiral catalyst.
27. The process as claimed in one of claims 25 and 26, wherein the reducing agent is an achiral reducing agent, preferably 1. a borane-sulfide complex, more preferably borane-dimethyl sulfide or borane-1,4-thioxane complex;
2. a borane etherate, for example boron-tetrahydrofuran complex;
3. catecholborane;
4. a borane-sulfide complex or a borane etherate or catecholborane in the presence of a Lewis acid, more preferably titanium chloride triisopropoxide (iPrO)3TiCl;
5. a borane-amine complex, more preferably borane-ammonia, borane-tert-butylamine, borane-N,N-diethylaniline, borane-N-ethyldiisopropylamine, borane-N-ethylmorpholine, borane-N-methylmorpholine, borane-morpholine, borane-piperidine, borane-pyridine, borane-triethylamine or borane-trimethylamine complexes;
6. a borane-amine complex in the presence of a Lewis acid, more preferably titanium chloride triisopropoxide (iPrO)3TiCl;
7. a borane-phosphine complex, more preferably borane-tributylphosphine or borane-triphenylphosphine complexes;
8. a combination of a borohydride, more preferably sodium borohydride or tetraalkylammonium borohydride, with a reagent which leads to in situ generation of borane, especially preferably sodium borohydride/iodine, sodium borohydride/boron trifluoride diethyletherate, sodium borohydride/chlorotrimethylsilane; tetraalkylammonium borohydridelalkyl halide (for example methyl iodide) in dichloromethane or the biphasic mixture of an alkyl bromide and a saturated aqueous solution of sodium borohydride and catalytic amounts of a quaternary opium salt as a phase transfer catalyst;
9. a borohydride of a mono- or bivalent metal cation, more preferably sodium borohydride, lithium borohydride or zinc borohydride, or a tetraalkylammonium borohydride, in the presence or absence of a cerium(III) salt as an additive;
10. diborane (B2H6), or a reducing agent comprising one or more optically active catalysts, preferably 1. a borohydride of a mono- or bivalent metal cation, more preferably sodium borohydride, in the presence of catalytic amounts of an optically active aldiminato cobalt(II) complex, for example (1S,2S)-N,N'-bis[3-oxo-2-(2,4,6-trimethylbenzoyl)butylidene]-1,2-diphenylethylenediaminato cobalt(II) (S)-MPAC, in the presence or absence of tetrahydrofurfuryl alcohol as a coligand;
2. a borohydride of a mono- or bivalent metal cation, more preferably sodium borohydride, catalyzed by a rhodium complex which results from the coordination of two molecules of optically pure 1,3-amino alcohol (II) per molecule of [(µ5)-pentamethylcyclopentadienyl]rhodium dichloride dimer;
3. CATHy.TM. - catalysts composed of the cyclopentadienylrhodium chloride dimer and chiral 1,2-amino alcohols.
2. a borane etherate, for example boron-tetrahydrofuran complex;
3. catecholborane;
4. a borane-sulfide complex or a borane etherate or catecholborane in the presence of a Lewis acid, more preferably titanium chloride triisopropoxide (iPrO)3TiCl;
5. a borane-amine complex, more preferably borane-ammonia, borane-tert-butylamine, borane-N,N-diethylaniline, borane-N-ethyldiisopropylamine, borane-N-ethylmorpholine, borane-N-methylmorpholine, borane-morpholine, borane-piperidine, borane-pyridine, borane-triethylamine or borane-trimethylamine complexes;
6. a borane-amine complex in the presence of a Lewis acid, more preferably titanium chloride triisopropoxide (iPrO)3TiCl;
7. a borane-phosphine complex, more preferably borane-tributylphosphine or borane-triphenylphosphine complexes;
8. a combination of a borohydride, more preferably sodium borohydride or tetraalkylammonium borohydride, with a reagent which leads to in situ generation of borane, especially preferably sodium borohydride/iodine, sodium borohydride/boron trifluoride diethyletherate, sodium borohydride/chlorotrimethylsilane; tetraalkylammonium borohydridelalkyl halide (for example methyl iodide) in dichloromethane or the biphasic mixture of an alkyl bromide and a saturated aqueous solution of sodium borohydride and catalytic amounts of a quaternary opium salt as a phase transfer catalyst;
9. a borohydride of a mono- or bivalent metal cation, more preferably sodium borohydride, lithium borohydride or zinc borohydride, or a tetraalkylammonium borohydride, in the presence or absence of a cerium(III) salt as an additive;
10. diborane (B2H6), or a reducing agent comprising one or more optically active catalysts, preferably 1. a borohydride of a mono- or bivalent metal cation, more preferably sodium borohydride, in the presence of catalytic amounts of an optically active aldiminato cobalt(II) complex, for example (1S,2S)-N,N'-bis[3-oxo-2-(2,4,6-trimethylbenzoyl)butylidene]-1,2-diphenylethylenediaminato cobalt(II) (S)-MPAC, in the presence or absence of tetrahydrofurfuryl alcohol as a coligand;
2. a borohydride of a mono- or bivalent metal cation, more preferably sodium borohydride, catalyzed by a rhodium complex which results from the coordination of two molecules of optically pure 1,3-amino alcohol (II) per molecule of [(µ5)-pentamethylcyclopentadienyl]rhodium dichloride dimer;
3. CATHy.TM. - catalysts composed of the cyclopentadienylrhodium chloride dimer and chiral 1,2-amino alcohols.
28. The process as claimed in one of claims 25 to 27, wherein the reducing agent is a borane-sulfide complex, a borane etherate, sodium borohydride or an asymetric sodium borohydride reducing agent comprising an in situ catalyst which is obtained by the coordination of the [(µ5)-pentamethylcyclopentadienyl]rhodium dichloride dimer to the optically active 1,3-amino alcohol (II).
29. The process as claimed in one of claims 25 to 28, wherein the reducing agent is a borane-dimethyl sulfide or borane-tetrahydrofuran complex.
30.The process as claimed in one of claims 25 to 29, wherein the compound of the formula (II) is worked up by acidic solvolysis and/or by crystallization.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10219987A DE10219987A1 (en) | 2002-05-03 | 2002-05-03 | Optically active β-amino ketones, optically active 1,3-amino alcohols and process for their preparation |
| DE10219987.6 | 2002-05-03 | ||
| PCT/EP2003/004127 WO2003093259A1 (en) | 2002-05-03 | 2003-04-22 | OPTICALLY ACTIVE β-AMINOKETONES, OPTICALLY ACTIVE 1,3-AMINOALCOHOLS AND METHOD FOR THE PRODUCTION THEREOF |
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| CA2484685A1 true CA2484685A1 (en) | 2003-11-13 |
| CA2484685C CA2484685C (en) | 2012-01-03 |
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| CA2484685A Expired - Fee Related CA2484685C (en) | 2002-05-03 | 2003-04-22 | Optically active .beta.-aminoketones, optically active 1,3-amino alcohols and method for the production thereof |
Country Status (11)
| Country | Link |
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| EP (1) | EP1504002B1 (en) |
| JP (1) | JP4510614B2 (en) |
| AR (1) | AR039508A1 (en) |
| AU (1) | AU2003224108B9 (en) |
| BR (1) | BR0309871A (en) |
| CA (1) | CA2484685C (en) |
| DE (1) | DE10219987A1 (en) |
| IL (1) | IL164901A (en) |
| MX (1) | MXPA04010877A (en) |
| TW (1) | TW200408635A (en) |
| WO (1) | WO2003093259A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US9673406B2 (en) | 2009-05-20 | 2017-06-06 | Universal Display Corporation | Metal complexes with boron-nitrogen heterocycle containing ligands |
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| CN100410234C (en) * | 2003-04-25 | 2008-08-13 | 东亚合成株式会社 | Asymmetric-synthesis catalyst based on chiral broensted acid and method of asymmetric synthesis with the catalyst |
| JPWO2005070875A1 (en) * | 2004-01-26 | 2007-09-06 | 高砂香料工業株式会社 | Method for producing amines |
| DE102005056856A1 (en) * | 2005-11-28 | 2007-05-31 | Sanofi-Aventis Deutschland Gmbh | Deuteriation of organic compounds, useful in research centers, comprises dissolving/suspending a compound in deuterium oxide and exposing the compound in catalyst mixture comprising transition metal and deuteride and/or hydride |
| CN112939008B (en) * | 2019-11-26 | 2022-09-16 | 中国科学院大连化学物理研究所 | Rapid synthesis method of Beta molecular sieve with controllable particle size |
| CN116041724B (en) * | 2023-02-23 | 2024-03-01 | 天津工业大学 | Porous chiral metal-organic framework material and preparation method and application thereof |
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| DE19845402B4 (en) * | 1998-10-02 | 2005-04-07 | Aventis Pharma Deutschland Gmbh | Heterocyclic substituted propanolamine derivatives, process for their preparation, pharmaceutical compositions containing them and their use |
| DE19845405C2 (en) * | 1998-10-02 | 2000-07-13 | Aventis Pharma Gmbh | Aryl-substituted propanolamine derivatives and their use |
| DE19845406C2 (en) * | 1998-10-02 | 2001-10-18 | Aventis Pharma Gmbh | Substituted 1,3-diaryl-2-pyridin-2-yl-3- (pyridin-2-ylamino) propanol derivatives, process for their preparation, medicaments containing these compounds and their use |
-
2002
- 2002-05-03 DE DE10219987A patent/DE10219987A1/en not_active Withdrawn
-
2003
- 2003-04-22 EP EP03720507A patent/EP1504002B1/en not_active Expired - Lifetime
- 2003-04-22 AU AU2003224108A patent/AU2003224108B9/en not_active Ceased
- 2003-04-22 JP JP2004501398A patent/JP4510614B2/en not_active Expired - Fee Related
- 2003-04-22 CA CA2484685A patent/CA2484685C/en not_active Expired - Fee Related
- 2003-04-22 BR BR0309871-0A patent/BR0309871A/en not_active Application Discontinuation
- 2003-04-22 WO PCT/EP2003/004127 patent/WO2003093259A1/en active Application Filing
- 2003-04-22 MX MXPA04010877A patent/MXPA04010877A/en active IP Right Grant
- 2003-04-30 TW TW092110083A patent/TW200408635A/en unknown
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US9673406B2 (en) | 2009-05-20 | 2017-06-06 | Universal Display Corporation | Metal complexes with boron-nitrogen heterocycle containing ligands |
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| MXPA04010877A (en) | 2005-01-25 |
| JP2005537229A (en) | 2005-12-08 |
| JP4510614B2 (en) | 2010-07-28 |
| EP1504002B1 (en) | 2012-12-19 |
| IL164901A (en) | 2010-05-31 |
| BR0309871A (en) | 2005-04-26 |
| AU2003224108A1 (en) | 2003-11-17 |
| WO2003093259A1 (en) | 2003-11-13 |
| EP1504002A1 (en) | 2005-02-09 |
| IL164901A0 (en) | 2005-12-18 |
| AU2003224108B2 (en) | 2009-01-08 |
| TW200408635A (en) | 2004-06-01 |
| CA2484685C (en) | 2012-01-03 |
| AU2003224108B9 (en) | 2009-05-21 |
| DE10219987A1 (en) | 2004-04-08 |
| AR039508A1 (en) | 2005-02-23 |
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