Patent ID: 6686477
Filing Date: 2004-02-03
Classification: C07B,C07C,C07D,C07F,Y02P

Abstract:
A method for producing the compound of formula VII, comprising hydrogenating an enamide having the formula VI with hydrogen in the presence of a catalyst comprised of a chiral ligand/metal complex to asymmetrically hydrogenate the carbon-carbon double bond of the enamide wherein R1, R2, and R3 are, independently, hydrogen, a branched or straight chain C1 to C20 alkyl group; a branched or straight chain C1 to C20 alkyl group substituted with one to three groups selected from cyano, hydroxy, aryl, halogen, â€”OR, â€”CO2R, and â€”OCOR; a C3 to C8 cycloalkyl group; a C3 to C9 cycloalkyl group substituted with one to three groups selected from cyano, hydroxy, aryl, halogen, â€”OR, â€”CO2 R, and â€”OCOR; a C6 to C20 aryl group; a C6 to C20 aryl group substituted with one to three groups selected from C1-C6-alkyl, C6-C10 aryl, C1-C6-alkoxy, halogen, carboxy, cyano, C1-C6-alkanoyloxy, C1-C6-alkylthio, C1-C6-alkylsulfonyl, trifluoromethyl, hydroxy, C2-C6-alkoxycarbonyl, C2-C6-alkanoylamino, â€”ORâ€², SRâ€², â€”SO2Râ€², â€”NHSO2Râ€² and â€”NHCO2Râ€²; or a 5- or 6-membered aromatic ring containing 1 to 3 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, which may be substituted with up to three groups selected from C1-C6-alkyl, C1-C6-alkoxy, halogen, C1-C6-alkylthio, aryl, arylthio, aryloxy, C2-C6-alkoxycarbonyl and C1-C6-alkanoylamino; R is C1-C6-alkyl; Râ€² is phenyl, naphthyl, or phenyl or naphthyl; n is 2; the stereochemistry at carbon a is substantially R or S; and wherein the chiral ligand of the chiral ligand/metal complex comprises a substantially enantiomerically pure bis-phosphine compound comprising a substantially enantiomerically pure chiral backbone linking two phosphine groups, wherein one of the phosphine groups has three phosphorus-carbon bonds and the other phosphine group has two phosphorus-carbon bonds and one phosphorus-nitrogen bond wherein the nitrogen is part of the chiral backbone.