3-(methylamino)-1-phenylpropan-1-ol
Numéro de catalogue B195923
Poids moléculaire: 165.23 g/mol
Clé InChI: XXSDCGNHLFVSET-UHFFFAOYSA-N
Attention: Uniquement pour un usage de recherche. Non destiné à un usage humain ou vétérinaire.
Patent
US05166437
Procedure details
An improved process for the preparation in a superior yield of the hydrochloride salt of N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine of formula (I), ##STR9## said process comprising catalytically hydrogenating 2-benzoyl-1-(N-benzyl-N-methyl)ethylamine base of formula (II), ##STR10## with the aid of a catalyst selected from the group consisting of Pt/C, Pd/C and Pd-Pt/C in ethyl acetate at a hydrogen pressure of 1 to 20 bar and at a temperature of approximately 20° to 100° C. whereby 1-phenyl-3-(N-methylamino)-propan-1-ol of formula (III) is formed, ##STR11## and selectively etherifying the compound of formula (III) with 1-chloro-4-trifluoromethylbenzene of formula (IV), ##STR12## in a solvent selected from the group consisting of N-methylpyrrolidone and dimethylsulfoxide in the presence of potassium t-butoxide, whereby N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine is formed in a yield greater than 85 percent of the theoretical value and is converted to the hydrochloride salt.
[Compound]
Name
( IV )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
[Compound]
Name
hydrochloride salt
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( I )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
2-benzoyl-1-(N-benzyl-N-methyl)ethylamine
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eight
[Compound]
Name
( II )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
Yield
85%
Identifiers
|
REACTION_CXSMILES
|
[H][H].[C:3]1([CH:9]([OH:14])[CH2:10][CH2:11][NH:12][CH3:13])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.CC(C)([O-])C.[K+]>C(OCC)(=O)C.[Pt].[Pd].[Pd].[Pt].CS(C)=O.CN1CCCC1=O>[CH3:13][NH:12][CH2:11][CH2:10][CH:9]([O:14][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1 |f:3.4,8.9|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClC1=CC=C(C=C1)C(F)(F)F
|
Step Two
[Compound]
|
Name
|
( IV )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CC(C)([O-])C.[K+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
C(C)(=O)OCC
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pt]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pd]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pd].[Pt]
|
Step Five
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CS(=O)C
|
Step Six
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CN1C(CCC1)=O
|
Step Seven
[Compound]
|
Name
|
hydrochloride salt
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( I )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
[Compound]
|
Name
|
2-benzoyl-1-(N-benzyl-N-methyl)ethylamine
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Nine
[Compound]
|
Name
|
( II )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is formed
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CNCCC(C1=CC=CC=C1)OC1=CC=C(C=C1)C(F)(F)F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 85% |
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
Patent
US05166437
Procedure details
An improved process for the preparation in a superior yield of the hydrochloride salt of N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine of formula (I), ##STR9## said process comprising catalytically hydrogenating 2-benzoyl-1-(N-benzyl-N-methyl)ethylamine base of formula (II), ##STR10## with the aid of a catalyst selected from the group consisting of Pt/C, Pd/C and Pd-Pt/C in ethyl acetate at a hydrogen pressure of 1 to 20 bar and at a temperature of approximately 20° to 100° C. whereby 1-phenyl-3-(N-methylamino)-propan-1-ol of formula (III) is formed, ##STR11## and selectively etherifying the compound of formula (III) with 1-chloro-4-trifluoromethylbenzene of formula (IV), ##STR12## in a solvent selected from the group consisting of N-methylpyrrolidone and dimethylsulfoxide in the presence of potassium t-butoxide, whereby N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine is formed in a yield greater than 85 percent of the theoretical value and is converted to the hydrochloride salt.
[Compound]
Name
( IV )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
[Compound]
Name
hydrochloride salt
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( I )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
2-benzoyl-1-(N-benzyl-N-methyl)ethylamine
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eight
[Compound]
Name
( II )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
Yield
85%
Identifiers
|
REACTION_CXSMILES
|
[H][H].[C:3]1([CH:9]([OH:14])[CH2:10][CH2:11][NH:12][CH3:13])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.CC(C)([O-])C.[K+]>C(OCC)(=O)C.[Pt].[Pd].[Pd].[Pt].CS(C)=O.CN1CCCC1=O>[CH3:13][NH:12][CH2:11][CH2:10][CH:9]([O:14][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1 |f:3.4,8.9|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClC1=CC=C(C=C1)C(F)(F)F
|
Step Two
[Compound]
|
Name
|
( IV )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CC(C)([O-])C.[K+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
C(C)(=O)OCC
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pt]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pd]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pd].[Pt]
|
Step Five
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CS(=O)C
|
Step Six
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CN1C(CCC1)=O
|
Step Seven
[Compound]
|
Name
|
hydrochloride salt
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( I )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
[Compound]
|
Name
|
2-benzoyl-1-(N-benzyl-N-methyl)ethylamine
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Nine
[Compound]
|
Name
|
( II )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is formed
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CNCCC(C1=CC=CC=C1)OC1=CC=C(C=C1)C(F)(F)F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 85% |
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
Patent
US05166437
Procedure details
An improved process for the preparation in a superior yield of the hydrochloride salt of N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine of formula (I), ##STR9## said process comprising catalytically hydrogenating 2-benzoyl-1-(N-benzyl-N-methyl)ethylamine base of formula (II), ##STR10## with the aid of a catalyst selected from the group consisting of Pt/C, Pd/C and Pd-Pt/C in ethyl acetate at a hydrogen pressure of 1 to 20 bar and at a temperature of approximately 20° to 100° C. whereby 1-phenyl-3-(N-methylamino)-propan-1-ol of formula (III) is formed, ##STR11## and selectively etherifying the compound of formula (III) with 1-chloro-4-trifluoromethylbenzene of formula (IV), ##STR12## in a solvent selected from the group consisting of N-methylpyrrolidone and dimethylsulfoxide in the presence of potassium t-butoxide, whereby N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine is formed in a yield greater than 85 percent of the theoretical value and is converted to the hydrochloride salt.
[Compound]
Name
( IV )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
[Compound]
Name
hydrochloride salt
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( I )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
2-benzoyl-1-(N-benzyl-N-methyl)ethylamine
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eight
[Compound]
Name
( II )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
Yield
85%
Identifiers
|
REACTION_CXSMILES
|
[H][H].[C:3]1([CH:9]([OH:14])[CH2:10][CH2:11][NH:12][CH3:13])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.CC(C)([O-])C.[K+]>C(OCC)(=O)C.[Pt].[Pd].[Pd].[Pt].CS(C)=O.CN1CCCC1=O>[CH3:13][NH:12][CH2:11][CH2:10][CH:9]([O:14][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1 |f:3.4,8.9|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
ClC1=CC=C(C=C1)C(F)(F)F
|
Step Two
[Compound]
|
Name
|
( IV )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CC(C)([O-])C.[K+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
C(C)(=O)OCC
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pt]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pd]
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
catalyst
|
|
Smiles
|
[Pd].[Pt]
|
Step Five
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CS(=O)C
|
Step Six
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CN1C(CCC1)=O
|
Step Seven
[Compound]
|
Name
|
hydrochloride salt
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( I )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
[Compound]
|
Name
|
2-benzoyl-1-(N-benzyl-N-methyl)ethylamine
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Nine
[Compound]
|
Name
|
( II )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C1(=CC=CC=C1)C(CCNC)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
is formed
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CNCCC(C1=CC=CC=C1)OC1=CC=C(C=C1)C(F)(F)F
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 85% |
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
