Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1998-09-25
1999-10-19
Burn, Brian M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564381, 564373, C07C20984
Patent
active
059691867
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for racemizing optically active amines of the formula (1) below which comprises reacting said optically active amine with a complex of an alkali metal and a polycyclic aromatic hydrocarbon.
BACKGROUND ART
Useful as optical resolution agents, as asymmetric auxiliary agents, as ligands for metals in an asymmetric reaction, or as intermediates for pharmaceuticals are optically active amines of the following formula (1): ##STR1## wherein R.sup.1 is an unsubstituted aryl group; an aryl group substituted with one to five substituents selected from the group consisting of C.sub.1 -C.sub.4 alkyl groups, C.sub.1 -C.sub.4 alkoxy groups and halogen atoms; or an unsubstituted or substituted heterocyclic group; substituted with one to three aryl groups; a C.sub.1 -C.sub.8 alkoxy group; a C.sub.1 -C.sub.8 alkoxy group substituted with one to three aryl groups; an unsubstituted aryloxy group; an aryloxy group substituted with one to five substituents selected from the group consisting of halogen atoms, C.sub.1 -C.sub.4 alkyl groups optionally substituted with one to three halogen atoms and C.sub.1 -C.sub.4 alkoxy groups optionally substituted with one to three halogen atoms; or substituents selected from the group consisting of C.sub.1 -C.sub.4 alkyl groups, C.sub.1 -C.sub.4 alkoxy groups and halogen atoms; or an unsubstituted or substituted heterocyclic group; provided that these unsubstituted and substituted aryl and heterocyclic groups are not identical to R.sup.1 ; hydrogen atoms, C.sub.1 -C.sub.4 alkyl groups, C.sub.1 -C.sub.4 alkyl groups substituted with one to three aryl groups, or C.sub.1 -C.sub.4 alkyl-CO-groups;
In particular, the optically active amine of the formula (1) wherein R.sup.1 is phenyl, R.sup.2 is isopropyl, R.sup.3 and R.sup.4 are both hydrogen atoms, and A is methylene, i.e., optically active 3-methyl-2-phenylbutylamine (PBA) is a useful compound as an optical resolution agent. The compound is used as an optical resolution agent for obtaining only one optically active isomer from racemic ibuprofen [2-(4-isobutylphenyl)propionic acid], ketoprofen [2-(3-benzoylphenyl)propionic acid] or the like, the isomer being useful as an anti-inflammatory, analgesic, antipyretic or antirheumatic agent [Japanese Patent Publication (Kokai) Nos. 229986/1993 and 151344/1996].
At present, optically active PBA can be obtained by resolving racemic PBA with an optically active acid such as mandelic acid [Japanese Patent Publication (Kokai) No. 172853/1986] or by selectively hydrolyzing an amide of PBA with an enzyme [Japanese Patent Application No. 215722/1995]. A method utilizing a reaction in which a nitrile undergoes optically selective hydration catalyzed by an enzyme has also been developed [Japanese Patent Publication (Kokai) No. 303496/1995].
If an optically active compound having either one of the steric configurations is desired and if one intends to obtain the optically active compound by optical resolution of its racemate, in general, the desired optically active compound is obtained only in 50% yield even at maximum, and not less than 50% of undesired optically active compound is discarded. Accordingly, if one intends to obtain an optically active compound by an optical resolution process, it is important to develop a process for racemization and/or inversion of the steric configuration of the undesired optically active compound so as to increase the yield of the desired optically active compound.
A number of processes for racemizing an amine compound in which a carbon atom at the .alpha.-position of the amino group is an asymmetric one have been developed, including, amongst others, a process of heating the amine compound under an atmosphere of pressurized hydrogen with a catalyst for catalytic reduction such as Raney nickel, Raney cobalt or the like [Japanese Patent Publication (Kokai) No. 185943/1988], a process utilizing an imine formed by a reaction of the amine compound with a carbonyl compound [Japanese Patent Publication (Kokai) Nos. 238
REFERENCES:
patent: 3970700 (1976-07-01), Nagase et al.
patent: 4252744 (1981-02-01), Bison et al.
patent: 4859771 (1989-08-01), Reider et al.
patent: 5723672 (1998-03-01), Nagata et al.
Hirayama Yoshihiko
Inoue Toru
Burn Brian M.
Nagase & Company, Ltd.
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