Patent ID: 6069245
Filing Date: 2000-05-30
Classification: C07D,Y02P

Abstract:
A process for the manufacture of compounds of the formula ##STR16## wherein R.sup.1 and R.sup.2 are independently an acyl residue of an aromatic carboxylic acid wherein the aromatic carboxylic acid is selected from the group consisting of benzoic acid; benzoic acid substituted by hydroxy, halogen, lower-alkyl or lower alkoxy, benzoyl; and benzoyl substitited by fluorine, lower-alkyl or lower-alkoxy; comprising:a) asymmetrically hydrogenating a compound of the formula ##STR17## wherein R.sup.3 is lower-alkyl and HX is an acid, in the presence of a ruthenium-diphosphine complex catalyst having a formula selected from the group consisting of(RuL).sup.2+ (X.sup.0).sub.2 III-a(RuLX.sup.2).sup.2+ (X.sup.0).sub.2 III-b(RuLX.sup.1 X.sup.2).sup.+ X.sup.3 III-candRuL(X.sup.4).sub.2 III-dwhereinX.sup.0 is selected from the group consisting of BF.sub.4.sup.-, ClO.sub.4.sup.-, B(phenyl).sub.4.sup.-,SbF.sub.6.sup.-, PF.sub.6.sup.- and Z.sup.1 --SO.sub.3.sup.- ;X.sup.1 is halide;X.sup.2 is benzene, hexamethylbenzene or p-cymene;X.sup.3 is selected from the group consisting of halide, ClO.sub.4.sup.-, B(phenyl).sub.4.sup.-, SbF.sub.6.sup.-, PF.sub.6.sup.-, Z.sup.1 --SO.sub.3.sup.- and BF.sub.4.sup.- ;X.sup.4 is selected from the group consisting of Z.sup.2 --COO.sup.-, Z.sup.3 --SO.sub.3.sup.-, allyl and CH.sub.3 COCH.dbd.C(CH.sub.3)O--;Z.sup.1 is halogenated lower alkyl or halogenated phenyl;Z.sup.2 is selected from the group consisting of lower alkyl, phenyl, halogenated lower alkyl and halogenated phenyl;Z.sup.3 is lower alkyl or phenyl; andL is an optically active atropisomeric, diphosphine ligand; to a compound of the formula ##STR18## b) providing an amino protecting group R.sup.4 to the amino moiety of the compound of formula IV;c) saponifying the compound of formula IV after step b), forming a compound of the formula ##STR19## d) converting the compound of formula V into a compound of the formula ##STR20## e) hydrolyzing the compound of formula VI into a compound of the formula ##STR21## f) where R.sup.1 and R.sup.2 are the same, N- and O-acylating the compound of formula VII with an aromatic carboxylic acid of the formula R.sup.1 OH or R.sup.2 OH to form a compound of the formula ##STR22## where R.sup.1 and R.sup.2 are different, first N-acylating the compound of formula VII with an aromatic carboxylic acid of formula R.sup.1 OH and then O-acylating the resulting compound with an aromatic carboxylic acid of the formula R.sup.2 OH to form a compound of formula XII; andg) cleaving off the protective group on the compound of formula XII, to form the compound of formula I.