Process for preparing a substituted dimethyl-(3-arylbutyl)amine compound by homogeneous catalysis

摘要

Compounds of the formula II;
can be hydrogenated to the corresponding butane derivatives in the presence of homogeneous cataslysts composed of metal salts or complexes containing metals selected from the group consisting of Rh, Ir, and Ru and preferably containing diphosphine ligands, with, in addition, excellent optical yields being achieved when one of R2 and R3 is not a hydrogen atom and the diphosphine ligand is chiral.

主权项

1. A process for preparing a substituted dimethyl-(3-arylbutyl)amine compound corresponding to formula III:wherein
R1, R1′, R2, R3 each independently denote —H or —C1-5-alkyl, R4, R4′, R5, R5′, R6 are identical or different and each represent —H, —OH, —C1-4-alkyl, —O—C1-4-alkyl, partly fluorinated or perfluorinated —C1-4-alkyl, partly fluorinated or perfluorinated —O—C1-4-alkyl, —O—CH2)n-phenyl where n is 1, 2 or 3, F, Cl or OR8, or two adjacent radicals R4 and R5, R5 and R6, R6 and R5′ or R5′ and R4′ represent a group —OCH═CHO—, —CH═C(R9)—O—, —CH═C(R9)—S— or —CH═CH—C(OR10)═CH— as part of a ring, with the proviso that the other particular radicals R6, R5 and R4′, R4, R5′ and R6′, R4, R5 and R4′ or R4, R5 and R6 have the abovementioned meaning, R8 denotes —CO—C1-5-alkyl, —PO(O—C1-4-alkyl)2, —CO—C6H4—R11, —CO(O—C1-5-alkyl), —CO—CHR12—NHR13, —CO—NH—C6H3—(R14)2 or an unsubstituted or substituted pyridyl, thienyl, thiazolyl or phenyl group, R9 denotes —H or —C1-4-alkyl, R10denotes —H or —C1-3-alkyl, R11denotes —OC(O)—C1-3-alkyl in the ortho-position or —CH2—N—(R15)2 in the meta- or para-position, wherein R15 in each case denotes —C1-4-alkyl or the two radicals R15 together with the bridging nitrogen atom form a 4-morpholino radical, R12 and R13 are identical or different and each represent —H, —C1-6-alkyl or —C3-8-cycloalkyl, or R12 and R13 together denote —(CH2)3-8— as part of a ring, and R14 denotes —H, —OH, —C1-7-alkyl, partly fluorinated or perfluorinated —C1-7-alkyl, —OC1-7-alkyl, -phenyl, —O-aryl, —F or —Cl, with the proviso that R14 may be identical or different,said process comprising:
(a) choosing a homogeneous catalyst comprising a soluble rhodium salt or rhodium complex including an appropriate chiral diphosphine ligand with two secondary phosphine groups to prepare a specific diastereomer of a compound of formula III in a ratio of greater than or equal to 70:30 in favor of the specific diastereomer; and (b) reacting a substituted dimethyl-(3-arylbut-3-enyl)amine compound corresponding to formula II: or a salt thereof,wherein
R1 and R3 are methyl, R1′ and R2 are H, R4, R4′, R5′, and R6 are H, and R5 is OCH3,in the presence of hydrogen and the homogeneous catalyst having the appropriate chiral diphosphine ligand,wherein the chiral diphosphine ligands is:to prepare the specific diastereomer of the compound of formula III in the ratio of greater than or equal to 70:30 in favor of the specific diastereomer.