(+)-Galanthamine
Katalognummer B192826
Molekulargewicht: 287.35 g/mol
InChI-Schlüssel: ASUTZQLVASHGKV-SUYBPPKGSA-N
Achtung: Nur für Forschungszwecke. Nicht für den menschlichen oder tierärztlichen Gebrauch.
Patent
US06018043
Procedure details
Lithium aluminium hydride (1M in ether, 1.2 ml, 1.20 mmol) was placed in a two necked round bottom flask fitted with a reflux condenser and nitrogen inlet. (-)-N-methy-ephedrine (0.23 g, 1.26 mmol) in ether (1 ml) was added dropwise and the solution was heated at reflux for 1 hour then cooled to room temperature. N-Ethyl-2-aminopyridine (0.31g, 2.52 mmol) in ether (1 ml) was added and the bright yellow solution was heated under reflux for a further 1 hour. The solution was cooled to -78° C. and solid (+) narwedine (97% e.e) (0.10 g, 0.35 mmol) was added. The suspension was warmed to 0° C., stirred for 20 hours and then allowed to warm to room temperature over 1 hour. The reaction was quenched 2M potassium carbonate (10 ml). The mixture was extracted into ethyl acetate (2×10 ml) and then the combined organic layer was washed with water (5 ml) and brine (5 ml) and dried over magnesium sulphate. Filtration and evaporation gave an orange oil which was shown by NMR and GC-MS to contain galanthamine and epigalanthamine in a 1:1 mixture. Flash chromatography on silica in dichloromethane-methanol 10:1 yielded (+) galanthamine (98% e.e.) (30% yield) and (+)-epigalanthamine (95% e.e) (26% yield). ##STR3##
Name
dichloromethane methanol
Quantity
0 (± 1) mol
Type
solvent
Reaction Step One
[Compound]
Name
(-)-N-methy-ephedrine
Quantity
0.23 g
Type
reactant
Reaction Step Three
Identifiers
|
REACTION_CXSMILES
|
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(N1C=CC=CC1N)C.[CH3:16][N:17]1[CH2:34][C:32]2=[C:33]3[C:28](=[C:29]([O:35][CH3:36])[CH:30]=[CH:31]2)[O:27][C@H:26]2[C@@:20]3([CH:21]=[CH:22][C:23]([CH2:25]2)=[O:24])[CH2:19][CH2:18]1.CN1CC2C=CC(OC)=C3C=2[C@]2([C@@H](O3)C[C@@H](O)C=C2)CC1.CN1CC2=C3C(=C(OC)C=C2)OC2C3(C=CC(O)C2)CC1>CCOCC.ClCCl.CO>[CH3:16][N:17]1[CH2:34][C:32]2=[C:33]3[C:28](=[C:29]([O:35][CH3:36])[CH:30]=[CH:31]2)[O:27][C@H:26]2[C@@:20]3([CH:21]=[CH:22][C@@H:23]([OH:24])[CH2:25]2)[CH2:19][CH2:18]1 |f:0.1.2.3.4.5,11.12|
|
Inputs
Step One
|
Name
|
dichloromethane methanol
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
ClCCl.CO
|
Step Two
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
[H-].[Al+3].[Li+].[H-].[H-].[H-]
|
Step Three
[Compound]
|
Name
|
(-)-N-methy-ephedrine
|
|
Quantity
|
0.23 g
|
|
Type
|
reactant
|
|
Smiles
|
|
|
Name
|
|
|
Quantity
|
1 mL
|
|
Type
|
solvent
|
|
Smiles
|
CCOCC
|
Step Four
|
Name
|
|
|
Quantity
|
0.31 g
|
|
Type
|
reactant
|
|
Smiles
|
C(C)N1C(C=CC=C1)N
|
|
Name
|
|
|
Quantity
|
1 mL
|
|
Type
|
solvent
|
|
Smiles
|
CCOCC
|
Step Five
|
Name
|
|
|
Quantity
|
0.1 g
|
|
Type
|
reactant
|
|
Smiles
|
CN1CC[C@]23C=CC(=O)C[C@H]2OC4=C(C=CC(=C34)C1)OC
|
Step Six
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN1CC[C@@]23C=C[C@@H](C[C@@H]2OC=4C3=C(C=CC4OC)C1)O
|
Step Seven
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN1CCC23C=CC(CC2OC4=C(C=CC(=C34)C1)OC)O
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
stirred for 20 hours
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
fitted with a reflux condenser and nitrogen inlet
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the solution was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux for 1 hour
|
|
Duration
|
1 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the bright yellow solution was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
under reflux for a further 1 hour
|
|
Duration
|
1 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The solution was cooled to -78° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The suspension was warmed to 0° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
to warm to room temperature over 1 hour
|
|
Duration
|
1 h
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The reaction was quenched 2M potassium carbonate (10 ml)
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
The mixture was extracted into ethyl acetate (2×10 ml)
|
WASH
|
Type
|
WASH
|
|
Details
|
the combined organic layer was washed with water (5 ml) and brine (5 ml)
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over magnesium sulphate
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
Filtration and evaporation
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
gave an orange oil which
|
Outcomes
Product
Details
Reaction Time |
20 h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN1CC[C@]23C=C[C@H](C[C@H]2OC4=C(C=CC(=C34)C1)OC)O
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 30% |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 26% |
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
US06018043
Procedure details
Lithium aluminium hydride (1M in ether, 1.2 ml, 1.20 mmol) was placed in a two necked round bottom flask fitted with a reflux condenser and nitrogen inlet. (-)-N-methy-ephedrine (0.23 g, 1.26 mmol) in ether (1 ml) was added dropwise and the solution was heated at reflux for 1 hour then cooled to room temperature. N-Ethyl-2-aminopyridine (0.31g, 2.52 mmol) in ether (1 ml) was added and the bright yellow solution was heated under reflux for a further 1 hour. The solution was cooled to -78° C. and solid (+) narwedine (97% e.e) (0.10 g, 0.35 mmol) was added. The suspension was warmed to 0° C., stirred for 20 hours and then allowed to warm to room temperature over 1 hour. The reaction was quenched 2M potassium carbonate (10 ml). The mixture was extracted into ethyl acetate (2×10 ml) and then the combined organic layer was washed with water (5 ml) and brine (5 ml) and dried over magnesium sulphate. Filtration and evaporation gave an orange oil which was shown by NMR and GC-MS to contain galanthamine and epigalanthamine in a 1:1 mixture. Flash chromatography on silica in dichloromethane-methanol 10:1 yielded (+) galanthamine (98% e.e.) (30% yield) and (+)-epigalanthamine (95% e.e) (26% yield). ##STR3##
Name
dichloromethane methanol
Quantity
0 (± 1) mol
Type
solvent
Reaction Step One
[Compound]
Name
(-)-N-methy-ephedrine
Quantity
0.23 g
Type
reactant
Reaction Step Three
Identifiers
|
REACTION_CXSMILES
|
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(N1C=CC=CC1N)C.[CH3:16][N:17]1[CH2:34][C:32]2=[C:33]3[C:28](=[C:29]([O:35][CH3:36])[CH:30]=[CH:31]2)[O:27][C@H:26]2[C@@:20]3([CH:21]=[CH:22][C:23]([CH2:25]2)=[O:24])[CH2:19][CH2:18]1.CN1CC2C=CC(OC)=C3C=2[C@]2([C@@H](O3)C[C@@H](O)C=C2)CC1.CN1CC2=C3C(=C(OC)C=C2)OC2C3(C=CC(O)C2)CC1>CCOCC.ClCCl.CO>[CH3:16][N:17]1[CH2:34][C:32]2=[C:33]3[C:28](=[C:29]([O:35][CH3:36])[CH:30]=[CH:31]2)[O:27][C@H:26]2[C@@:20]3([CH:21]=[CH:22][C@@H:23]([OH:24])[CH2:25]2)[CH2:19][CH2:18]1 |f:0.1.2.3.4.5,11.12|
|
Inputs
Step One
|
Name
|
dichloromethane methanol
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
ClCCl.CO
|
Step Two
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
[H-].[Al+3].[Li+].[H-].[H-].[H-]
|
Step Three
[Compound]
|
Name
|
(-)-N-methy-ephedrine
|
|
Quantity
|
0.23 g
|
|
Type
|
reactant
|
|
Smiles
|
|
|
Name
|
|
|
Quantity
|
1 mL
|
|
Type
|
solvent
|
|
Smiles
|
CCOCC
|
Step Four
|
Name
|
|
|
Quantity
|
0.31 g
|
|
Type
|
reactant
|
|
Smiles
|
C(C)N1C(C=CC=C1)N
|
|
Name
|
|
|
Quantity
|
1 mL
|
|
Type
|
solvent
|
|
Smiles
|
CCOCC
|
Step Five
|
Name
|
|
|
Quantity
|
0.1 g
|
|
Type
|
reactant
|
|
Smiles
|
CN1CC[C@]23C=CC(=O)C[C@H]2OC4=C(C=CC(=C34)C1)OC
|
Step Six
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN1CC[C@@]23C=C[C@@H](C[C@@H]2OC=4C3=C(C=CC4OC)C1)O
|
Step Seven
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN1CCC23C=CC(CC2OC4=C(C=CC(=C34)C1)OC)O
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
stirred for 20 hours
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
fitted with a reflux condenser and nitrogen inlet
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the solution was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux for 1 hour
|
|
Duration
|
1 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the bright yellow solution was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
under reflux for a further 1 hour
|
|
Duration
|
1 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The solution was cooled to -78° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The suspension was warmed to 0° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
to warm to room temperature over 1 hour
|
|
Duration
|
1 h
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The reaction was quenched 2M potassium carbonate (10 ml)
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
The mixture was extracted into ethyl acetate (2×10 ml)
|
WASH
|
Type
|
WASH
|
|
Details
|
the combined organic layer was washed with water (5 ml) and brine (5 ml)
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over magnesium sulphate
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
Filtration and evaporation
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
gave an orange oil which
|
Outcomes
Product
Details
Reaction Time |
20 h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN1CC[C@]23C=C[C@H](C[C@H]2OC4=C(C=CC(=C34)C1)OC)O
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 30% |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 26% |
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
US06018043
Procedure details
Lithium aluminium hydride (1M in ether, 1.2 ml, 1.20 mmol) was placed in a two necked round bottom flask fitted with a reflux condenser and nitrogen inlet. (-)-N-methy-ephedrine (0.23 g, 1.26 mmol) in ether (1 ml) was added dropwise and the solution was heated at reflux for 1 hour then cooled to room temperature. N-Ethyl-2-aminopyridine (0.31g, 2.52 mmol) in ether (1 ml) was added and the bright yellow solution was heated under reflux for a further 1 hour. The solution was cooled to -78° C. and solid (+) narwedine (97% e.e) (0.10 g, 0.35 mmol) was added. The suspension was warmed to 0° C., stirred for 20 hours and then allowed to warm to room temperature over 1 hour. The reaction was quenched 2M potassium carbonate (10 ml). The mixture was extracted into ethyl acetate (2×10 ml) and then the combined organic layer was washed with water (5 ml) and brine (5 ml) and dried over magnesium sulphate. Filtration and evaporation gave an orange oil which was shown by NMR and GC-MS to contain galanthamine and epigalanthamine in a 1:1 mixture. Flash chromatography on silica in dichloromethane-methanol 10:1 yielded (+) galanthamine (98% e.e.) (30% yield) and (+)-epigalanthamine (95% e.e) (26% yield). ##STR3##
Name
dichloromethane methanol
Quantity
0 (± 1) mol
Type
solvent
Reaction Step One
[Compound]
Name
(-)-N-methy-ephedrine
Quantity
0.23 g
Type
reactant
Reaction Step Three
Identifiers
|
REACTION_CXSMILES
|
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(N1C=CC=CC1N)C.[CH3:16][N:17]1[CH2:34][C:32]2=[C:33]3[C:28](=[C:29]([O:35][CH3:36])[CH:30]=[CH:31]2)[O:27][C@H:26]2[C@@:20]3([CH:21]=[CH:22][C:23]([CH2:25]2)=[O:24])[CH2:19][CH2:18]1.CN1CC2C=CC(OC)=C3C=2[C@]2([C@@H](O3)C[C@@H](O)C=C2)CC1.CN1CC2=C3C(=C(OC)C=C2)OC2C3(C=CC(O)C2)CC1>CCOCC.ClCCl.CO>[CH3:16][N:17]1[CH2:34][C:32]2=[C:33]3[C:28](=[C:29]([O:35][CH3:36])[CH:30]=[CH:31]2)[O:27][C@H:26]2[C@@:20]3([CH:21]=[CH:22][C@@H:23]([OH:24])[CH2:25]2)[CH2:19][CH2:18]1 |f:0.1.2.3.4.5,11.12|
|
Inputs
Step One
|
Name
|
dichloromethane methanol
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
ClCCl.CO
|
Step Two
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
[H-].[Al+3].[Li+].[H-].[H-].[H-]
|
Step Three
[Compound]
|
Name
|
(-)-N-methy-ephedrine
|
|
Quantity
|
0.23 g
|
|
Type
|
reactant
|
|
Smiles
|
|
|
Name
|
|
|
Quantity
|
1 mL
|
|
Type
|
solvent
|
|
Smiles
|
CCOCC
|
Step Four
|
Name
|
|
|
Quantity
|
0.31 g
|
|
Type
|
reactant
|
|
Smiles
|
C(C)N1C(C=CC=C1)N
|
|
Name
|
|
|
Quantity
|
1 mL
|
|
Type
|
solvent
|
|
Smiles
|
CCOCC
|
Step Five
|
Name
|
|
|
Quantity
|
0.1 g
|
|
Type
|
reactant
|
|
Smiles
|
CN1CC[C@]23C=CC(=O)C[C@H]2OC4=C(C=CC(=C34)C1)OC
|
Step Six
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN1CC[C@@]23C=C[C@@H](C[C@@H]2OC=4C3=C(C=CC4OC)C1)O
|
Step Seven
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
CN1CCC23C=CC(CC2OC4=C(C=CC(=C34)C1)OC)O
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
stirred for 20 hours
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
fitted with a reflux condenser and nitrogen inlet
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the solution was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
at reflux for 1 hour
|
|
Duration
|
1 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
the bright yellow solution was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
under reflux for a further 1 hour
|
|
Duration
|
1 h
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The solution was cooled to -78° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The suspension was warmed to 0° C.
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
to warm to room temperature over 1 hour
|
|
Duration
|
1 h
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The reaction was quenched 2M potassium carbonate (10 ml)
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
The mixture was extracted into ethyl acetate (2×10 ml)
|
WASH
|
Type
|
WASH
|
|
Details
|
the combined organic layer was washed with water (5 ml) and brine (5 ml)
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried over magnesium sulphate
|
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
Filtration and evaporation
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
gave an orange oil which
|
Outcomes
Product
Details
Reaction Time |
20 h |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN1CC[C@]23C=C[C@H](C[C@H]2OC4=C(C=CC(=C34)C1)OC)O
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 30% |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| YIELD: PERCENTYIELD | 26% |
Source
|
Source
|
Open Reaction Database (ORD) |
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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. |
