Synthesis of (±)-2-((dimethylamino)methyl)-1-(aryl)cyclohexanols
AssigneeEuro-Celtique S.A.
InventorsRobert J. Kupper, Andreas Stumpf
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Abstract
Compositions comprising (±)-2-((dimethylamino)methyl)cyclohexanone, a transition-metal salt, and an organic solvent and methods of preparing (±)-cis-2-((dimethylamino)methyl)-1-(aryl)cyclohexanols, in particular (±)-cis-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol, are disclosed herein. In one embodiment, the (±)-2-((dimethylamino)methyl)cyclohexanone and transition-metal salt are in the form of a (±)-2-((dimethylamino)methyl)cyclohexanone:transition-metal salt complex. In another embodimemt, aryl is 3-methoxyphenyl.
Claims22
A method for synthesizing a (±)-cis-2-((dimethylamino)methyl)-1-(aryl) cyclohexanol and a (±)-trans-2-((dimethylamino)methyl)-1-(aryl)cyclohexanol in a ratio of at least about 85:15, comprising the steps of:
- (a) contacting (1) a composition comprising (±)-2-((dimethylamino)methyl) cyclohexanone, a transition metal-salt, and an organic solvent and (2) an aryl organometallic compound to provide a (±)-cis-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt and a (±)-trans-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt in a ratio of at least about 85:15;
- and
- (b) protonating the (±)-cis-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt and (±)-trans-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt,
- wherein aryl is a phenyl or naphthyl group optionally substituted with one or more R1 groups;
- R1 is selected from C1-C10 straight or branched chain alkyls, —OR2, halogen, —CF3, —NH2, NHR2, NR2R2;
- and
- each R2 is independently a phenyl, benzyl or C1-C10 straight or branched alkyl group.
A method for synthesizing a (±)-cis-2-((dimethylamino)methyl)-1-(aryl)cyclohexanol and a (±)-trans-2-((dimethylamino)methyl)-1-(aryl)cyclohexanol in a ratio of at least about 85:15, comprising the steps of:
- (a) contacting (1) a composition comprising (±)-2-((dimethylamino)methyl)cyclohexanone :transition metal-salt complex, and an organic solvent and (2) an aryl organometallic compound to provide a (±)-cis-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt and a (±)-trans-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt in a ratio of at least about 85:15;
- and
- (b) protonating the (±)-cis-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt and (±)-trans-2-((dimethylamino)methyl)-1-(aryl)cyclohexoxide salt,
- wherein aryl is a phenyl or naphthyl group optionally substituted with one or more R1 groups;
- R1 is selected from C1-C10 straight or branched chain alkyls, —OR2, halogen, —CF3, —NH2, NHR2, NR2R2;
- and
- each R2 is independently a phenyl, benzyl or C1-C10 straight or branched alkyl group.
Dependencies are inferred from the claim text.