(R)-Rivastigmine
Número de catálogo B1354846
Peso molecular: 250.34 g/mol
Clave InChI: XSVMFMHYUFZWBK-LLVKDONJSA-N
Atención: Solo para uso de investigación. No para uso humano o veterinario.
Patent
US07385076B2
Procedure details
The process of the present invention for example involves reacting 3-[1-(dimethylamino)ethyl]phenol with N-ethyl-N-methyl-4-nitrophenyl carbamate in the presence of potassium carbonate and dimethyl sulfoxide at a temperature ranging from about 80° C. to about 120° C. for about 30 to 40 hours, to form racemate of ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester in the free base form. This racemate is then resolved to obtain the (S)-ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester. The preferred method of resolution of the (S)-isomer from the racemate involves dissolving a mixture of the free base of the racemate and (+)-di-O, O′-p-toluoyl tartaric acid monohydrate in a 2:1 mixture of methanol:water by heating, collecting the precipitate on cooling by filtration, crystallizing the precipitate from a 2:1 mixture of ethanol:water, and obtaining the substantially pure (S)-isomer by partitioning it between 1N sodium hydroxide and a suitable organic solvent. The base may further be converted to its pharmaceutically acceptable acid addition salts, such as L(+)-tartrate salt.
[Compound]
Name
N-ethyl-N-methyl-4-nitrophenyl carbamate
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Identifiers
|
REACTION_CXSMILES
|
[CH3:1][N:2]([CH3:12])[CH:3]([C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)[CH3:4].[C:13](=[O:16])([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:12][N:2]([CH3:1])[CH:3]([C:5]1[CH:6]=[C:7]([O:11][C:13](=[O:16])[N:2]([CH2:3][CH3:4])[CH3:1])[CH:8]=[CH:9][CH:10]=1)[CH3:4] |f:1.2.3|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN(C(C)C=1C=C(C=CC1)O)C
|
Step Two
[Compound]
|
Name
|
N-ethyl-N-methyl-4-nitrophenyl carbamate
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C([O-])([O-])=O.[K+].[K+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CS(=O)C
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Outcomes
Product
Details
Reaction Time |
35 (± 5) h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(C(C)C=1C=C(C=CC1)OC(N(C)CC)=O)C
|
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
US07385076B2
Procedure details
The process of the present invention for example involves reacting 3-[1-(dimethylamino)ethyl]phenol with N-ethyl-N-methyl-4-nitrophenyl carbamate in the presence of potassium carbonate and dimethyl sulfoxide at a temperature ranging from about 80° C. to about 120° C. for about 30 to 40 hours, to form racemate of ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester in the free base form. This racemate is then resolved to obtain the (S)-ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester. The preferred method of resolution of the (S)-isomer from the racemate involves dissolving a mixture of the free base of the racemate and (+)-di-O, O′-p-toluoyl tartaric acid monohydrate in a 2:1 mixture of methanol:water by heating, collecting the precipitate on cooling by filtration, crystallizing the precipitate from a 2:1 mixture of ethanol:water, and obtaining the substantially pure (S)-isomer by partitioning it between 1N sodium hydroxide and a suitable organic solvent. The base may further be converted to its pharmaceutically acceptable acid addition salts, such as L(+)-tartrate salt.
[Compound]
Name
N-ethyl-N-methyl-4-nitrophenyl carbamate
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Identifiers
|
REACTION_CXSMILES
|
[CH3:1][N:2]([CH3:12])[CH:3]([C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)[CH3:4].[C:13](=[O:16])([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:12][N:2]([CH3:1])[CH:3]([C:5]1[CH:6]=[C:7]([O:11][C:13](=[O:16])[N:2]([CH2:3][CH3:4])[CH3:1])[CH:8]=[CH:9][CH:10]=1)[CH3:4] |f:1.2.3|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN(C(C)C=1C=C(C=CC1)O)C
|
Step Two
[Compound]
|
Name
|
N-ethyl-N-methyl-4-nitrophenyl carbamate
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C([O-])([O-])=O.[K+].[K+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CS(=O)C
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Outcomes
Product
Details
Reaction Time |
35 (± 5) h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(C(C)C=1C=C(C=CC1)OC(N(C)CC)=O)C
|
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
US07385076B2
Procedure details
The process of the present invention for example involves reacting 3-[1-(dimethylamino)ethyl]phenol with N-ethyl-N-methyl-4-nitrophenyl carbamate in the presence of potassium carbonate and dimethyl sulfoxide at a temperature ranging from about 80° C. to about 120° C. for about 30 to 40 hours, to form racemate of ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester in the free base form. This racemate is then resolved to obtain the (S)-ethylmethylcarbamic acid 3-[1-(dimethylamino)ethyl]phenyl ester. The preferred method of resolution of the (S)-isomer from the racemate involves dissolving a mixture of the free base of the racemate and (+)-di-O, O′-p-toluoyl tartaric acid monohydrate in a 2:1 mixture of methanol:water by heating, collecting the precipitate on cooling by filtration, crystallizing the precipitate from a 2:1 mixture of ethanol:water, and obtaining the substantially pure (S)-isomer by partitioning it between 1N sodium hydroxide and a suitable organic solvent. The base may further be converted to its pharmaceutically acceptable acid addition salts, such as L(+)-tartrate salt.
[Compound]
Name
N-ethyl-N-methyl-4-nitrophenyl carbamate
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
Identifiers
|
REACTION_CXSMILES
|
[CH3:1][N:2]([CH3:12])[CH:3]([C:5]1[CH:6]=[C:7]([OH:11])[CH:8]=[CH:9][CH:10]=1)[CH3:4].[C:13](=[O:16])([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:12][N:2]([CH3:1])[CH:3]([C:5]1[CH:6]=[C:7]([O:11][C:13](=[O:16])[N:2]([CH2:3][CH3:4])[CH3:1])[CH:8]=[CH:9][CH:10]=1)[CH3:4] |f:1.2.3|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN(C(C)C=1C=C(C=CC1)O)C
|
Step Two
[Compound]
|
Name
|
N-ethyl-N-methyl-4-nitrophenyl carbamate
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Three
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
C([O-])([O-])=O.[K+].[K+]
|
Step Four
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
CS(=O)C
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Outcomes
Product
Details
Reaction Time |
35 (± 5) h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(C(C)C=1C=C(C=CC1)OC(N(C)CC)=O)C
|
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. |
