Title:
PROCESS FOR THE PREPARATION OF SECONDARY AND TERTIARY AMINES
Document Type and Number:
WIPO Patent Application WO/2001/044162
Kind Code:
A1
Abstract:
N,N-disubstituted amines in which the amino nitrogen atom is bound to the carbon of an aromatic ring disubstituted in the positions ortho to the carbon atom, are prepared by allowing a primary amine and a compound in which an ortho, ortho-disubstituted aromatic compound carrying a nucleofuge substituent, to react in a basic environment in the presence of a catalytic palladium(0) complex and a ligand, the ratio of palladium complex to ligand being greater than at least 1:1. A typical embodiment involves the reaction of 2-methyl-6-ethylphenyl-trifluoromethylsulfonate and (S)-1-methoxy-2-aminopropane in the presence of bis(dibenzylideneacetone)palladium, tri-tert.-butylphosphine, and sodium tert.-butoxide to yield (S)-N-(1-methoxyprop-2-yl)-2-methyl-6-ethylphenylamine.
Inventors:
LIN SUE L (US)
ZHOU WEIXIA M (US)
MATCHAM GEORGE W (US)
ZHOU WEIXIA M (US)
MATCHAM GEORGE W (US)
Application Number:
PCT/US2000/026581
Publication Date:
June 21, 2001
Filing Date:
September 27, 2000
Export Citation:
Assignee:
CELGRO (US)
LIN SUE L (US)
ZHOU WEIXIA M (US)
MATCHAM GEORGE W (US)
LIN SUE L (US)
ZHOU WEIXIA M (US)
MATCHAM GEORGE W (US)
International Classes:
C07C209/10; C07C213/02; C07C217/08; (IPC1-7): C07C209/00
Foreign References:
| US4792622A | 1988-12-20 | |||
| US4757144A | 1988-07-12 |
Attorney, Agent or Firm:
Collins, Bruce M. (Collins Shepherd & Gould, P.A., 100 Thanet
Circle, Suite 30, Princeton NJ, US)
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Claims:
| 1. | A process for the preparation of an N, Ndisubstituted or N, N, Ntrisubstituted amine in which in one of the substituents the amino nitrogen atom is bound to the carbon atom of an aromatic ring disubstituted in the positions ortho to said carbon atom, which process comprises allowing (/) a primary or secondary amine and (il) a compound in which said carbon atom of the ortho, orthodisub stituted aromatic ring is bound to a nucleofuge, to react in a basic environment in the presence of (iii) a catalytic palladium (0) or nickel complex and (iv) a ligand in which the ratio of palladium (0) or nickel complex to ligand is greater than at least 1 : 1. |
| 2. | The process according to claim 1 wherein the reaction is conducted in an inert organic solvent. |
| 3. | The process according to claim 1 wherein a catalytic palladium (0) complex is employed and the ratio of palladium (0) complex to ligand is at least 4: 1. |
| 4. | The process according to claim 1 wherein a catalytic palladium (0) complex is employed and the ratio of palladium (0) complex to ligand is at least 4: 1. |
| 5. | The process according to claim 1 wherein the nucleofuge is the iodo, bromo, chloro, methanesulfonato, or trifluoromethanesulfonato radical. |
| 6. | The process according to claim 1 wherein said primary or secondary amine is an unsubstituted or substituted monoalkylamine. |
| 7. | The process according to claim 6 wherein said unsubstituted or substituted monoalkylamine is chiral. |
| 8. | The process according to claim 6 wherein said unsubstituted or substituted monoalkylamine is 1methoxy2aminopropane. |
| 9. | The process according to claim 8 wherein said 1methoxy2aminopropane is (S)1methoxy2aminopropane. |
| 10. | The process according to claim 1 wherein said aromatic ring is disubstituted by the same or different alkyl groups in the ortho positions. |
| 11. | The process according to claim 1 wherein the compound in which said car bon atom of the ortho, orthodisubstituted aromatic ring is bound to a nucleo fuge is 2,6dimethylphenyl bromide, 2,6dimethylphenyl chloride, 2,6dimethyl phenyl iodide, 2,6dimethylphenylmethylsulfonate, 2,6dimethylphenyltri fluoromethylsulfonate, 2methyl6ethylphenyl bromide, 2methyl6ethylphenyl chloride, 2methyl6ethylphenyl iodide, 2methyl6ethylphenylmethylsulfon ate, 2methyl6ethylphenyltrifluoromethylsulfonate, 2,6diethylphenyl bromide, 2,6diethylphenyl chloride, 2,6diethylphenyl iodide, 2,6diethylphenylmethyl sulfonate, or 2, 6diethylphenyltrifluoromethylsulfonate. |
| 12. | The process according to claim 1 wherein the catalytic palladium (O) or nickel complex is palladium chloride, palladium acetate, bis (trans, transdibenzyl ideneacetone) palladium, [1,1'bis (diphenylphosphino) ferrocene] dichloropalla dium, bis (triphenylphosphino) dichloropalladium, tetrakis (triphenylphosphine) palladium, bis (triphenylphosphino) dichloronickel, nickelcarbonyl, or bis (1,5 cyclooctadiene) nickel. |
| 13. | The process according to claim 12 wherein the catalytic palladium (0) or nickel complex is bis (dibenzylideneacetone) palladium or tetrakis (triphenyl phosphine) palladium. |
| 14. | The process according to claim 1 wherein the ligand is tri (tert.but yl) phosphine. 1,1'bis (diphenylphosphino) ferrocene, 2,2'bis (diphenylphos phino)1, 1'binaphthyl, tri (otolyl) phosphine, 4,12bis (diphenylphosphanyl) [2.2] paracyclophane, 1,1'bis (dipmethoxyphenylphosphino) ferrocene, 1, 1' bis (diptrifluoromethylphenylphosphino) ferrocene, 1,1'bis (d itolyl phosphino) ferrocene, or 2,2'bis (diphenylphosphino) diphenyl ether. |
| 15. | A process according to claim 1 for the preparation of N (1methoxyprop2 yl)2, 6dimethylphenylamine which comprises allowing (/) 1methoxy2aminopropane and (il) 2,6dimethylphenyl bromide, 2,6dimethylphenyl chloride, 2,6 dimethylphenyl iodide, 2, 6dimethylphenylmethylsulfonate, or 2,6 dimethylphenyltrifluoromethylsulfonate, to react in a basic environment in the presence of (iBl) palladium (0) or nickel complex catalyst which is palladium chlo ride, palladium acetate, bis (trans, transdibenzylideneacetone) palla dium, [1,1'bis (diphenylphosphino) ferrocene] dichloropalladium, bis (tri phenylphosphino) dichloropalladium, tetrakis (triphenylphosphine) pal ladium, bis (triphenylphosphino) dichloronickel, nickelcarbonyl, or bis (1,5cyclooctadiene) nickel, and (iv) a ligand which is tri (tert.butyl) phosphine, 1,1'bis (diphenylphos phino) ferrocene, 2,2'bis (diphenylphosphino)1, 1'binaphthyl, tri (o tolyl) phosphine, 4,12bis (diphenylphosphanyl) [2.2] paracyclophane, 1,1'bis (dipmethoxyphenylphosphino) ferrocene, 1,1'bis (diptrifluoro methylphenylphosphino) ferrocene, 1,1'bis (ditolylphosphino) ferrocene, or 2,2'bis (diphenylphosphino) diphenyl ether in which the ratio of palladium (0) complex to ligand is greater than at least 1: 1. |
| 16. | The process according to claim 15 wherein the catalytic palladium (0) or nickel complex is bis (dibenzylideneacetone) palladium or tetrakis (triphenyl phosphine) palladium. |
| 17. | A process according to claim 1 for the preparation of N (1methoxyprop2 yl)2methyl6ethylphenylamine which comprises allowing (/) 1methoxy2aminopropane and (il) 2methyl6ethylphenyl bromide, 2methyl6ethylphenyl chloride, 2methyl6ethylphenyl iodide, 2methyl6ethylphenylmethylsulfonate, or 2methyl6ethylphenyltrifluoromethylsulfonate, to react in a basic environment in the presence of ((iel) palladium (0) or nickel complex catalyst which is palladium chlo ride, palladium acetate, bis (trans, transdibenzylideneacetone) palla dium, [1,1'bis (diphenylphosphino) ferrocene] dichloropalladium, bis (triphenylphosphino) dichloropalladium, tetrakis (triphenylphosphine) palladium, bis (triphenylphosphino) dichloronickel, nickelcarbonyl, or bis (1, 5cyclooctadiene) nickel, and (iv) a ligand which is tri (tert.butyl) phosphine, 1,1'bis (diphenylphos phino) ferrocene, 2,2'bis (diphenylphosphino)1, 1'binaphthyl, tri (otol yl) phosphine, 4,12bis (diphenylphosphanyl) [2.2] paracyclophane, 1,1' bis (dipmethoxyphenylphosphino) ferrocene, 1,1'bis (diptrifluoro methylphenylphosphino) ferrocene, 1,1'bis (ditolylphosphino) ferrocene, or 2,2'bis (diphenylphosphino) diphenyl ether in which the ratio of palladium (0) complex to ligand is greater than at least 1: 1. |
| 18. | The process according to claim 17 wherein the catalytic palladium (0) or nickel complex is bis (dibenzylideneacetone) palladium or tetrakis (triphenyl phosphine) palladium. |
| 19. | A process according to claim 17 wherein (S)1methoxy2aminopropane is employed to yield (S)N (1methoxyprop2yl)2methyl6ethylphenylamine. |