Process for the preparation of chiral 1-aryl-2-aminopropanes
AssigneeCelgene Corporation
InventorsGeorge W. Matcham, Seujo Lee
Life of this patent
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Abstract
One chiral form of a 1-aryl-2-aminopropane is produced in preference to its enantiomer by allowing a 1-arylpropan-2-one to react with a 1-amino-1-phenylethane of predominantly one chiral form and reducing the resultant 1-(1-arylprop-2-ylideneimino)-1-phenylethane to yield phenylethane and a mixture of 1-aryl-2-aminopropanes in which one chiral form thereof is present in preference to its enantiomer. The mixture of 1-aryl-2-aminopropanes then is subjected to the action of an omega-amino acid transaminase which converts one of the two chiral forms of 1-aryl-2-aminopropane into the corresponding arylpropanone which can be separated from the remaining chiral form of the 1-aryl-2-aminopropane.
Claims9
The process of producing one chiral form of a 1-phenyl-2-aminopropane in preference to its enantiomer which comprises:
- (i) allowing a 1-phenylpropan-2-one to react with a 1-amino-1-phenylethane of predominantly one chiral form to produce the corresponding 1-(1-phenylprop-2-ylideneimino)-1-phenylethane;
- (ii) reducing the resultant 1-(1-phenylprop-2-ylideneimino)-1-phenylethane to yield phenylethane and a mixture of 1-phenyl-2-aminopropanes in which one chiral form thereof is present in preference to its enantiomer;
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- (iii) subjecting the mixture of 1-phenyl-2-aminopropanes, in an aqueous medium and in the presence of an amino acceptor, to the action of an omega-amino acid transaminase operable to enzymatically convert one chiral form of 1-phenyl-2-aminopropane into the corresponding 1-phenylpropanone and thereby increase the relative proportion of the chiral form of the 1-phenyl-2-aminopropane which is not enzymatically converted.
The process of producing one chiral form of a 1-phenyl-2-aminopropane in preference to its enantiomer which comprises:
- (i) allowing a 1-phenylpropan-2-one to react with a 1-amino-1-phenylethane of predominantly one chiral form to form a corresponding 1-(1-phenylprop-2-ylideneimino)-1-phenylethane of predominantly one chiral form;
- (ii) reducing the resultant 1-(1-phenylprop-2-ylideneimino)-1-phenylethane to form a diastereoisomeric mixture of the corresponding 1-(1-phenylprop-2-ylamino)-1-phenylethanes;
- (iii) subjecting the diastereoisomeric mixture of the 1-(1-phenylprop-2-ylamino)-1-phenylethanes, without further enantiomeric enrichment, to hydrogenolysis to yield a mixture of 1-phenyl-2-aminopropanes in which one chiral form thereof is formed in preference to its enantiomer and 1-amino-1-phenylethane;
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- (iv) subjecting the mixture of 1-phenyl-2-aminopropanes, in an aqueous medium and in the presence of an amino acceptor, to the action of an omega-amino acid transaminase operable to enzymatically convert one chiral form of 1-phenyl-2-aminopropane into the corresponding 1-phenylpropanone and thereby increase the relative proportion of the chiral form of the 1-phenyl-2-aminopropane which is not enzymatically converted.
Dependencies are inferred from the claim text.