(R)-(-)-citalopram
货号 B155561
分子量: 324.4 g/mol
InChI 键: WSEQXVZVJXJVFP-HXUWFJFHSA-N
注意: 仅供研究使用。不适用于人类或兽医用途。
Patent
US06660873B2
Procedure details
To a stirred solution of 5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran (0.5 g, 1.5 mmol) in dichloromethane (10 mL) was added an aqueous solution of potassium bisulfate and sodium hydroxide (19 mL; 0.2 M in K2S2O8, 3.8 mmol; 0.4 M in NaOH, 7.6 mmol), followed by an aqueous solution of nickel sulfate (1.5 mL, 40 mM, 61 μmol). The mixture was stirred vigorously for 4 days, and was then filtered through celite. The filtrate was partitioned between aqueous sulfuric acid (2 M) and toluene. The aqueous layer was separated, and the pH of the mixture was adjusted to >9 by the addition of aqueous ammonia solution (25% w/v). The solution was extracted with toluene, and this latter toluene extract was dried over magnesium sulfate and evaporated to give the free base of citalopram as a very pale yellow oil (0.35 g, 70%).
Name
5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran
Quantity
0.5 g
Type
reactant
Reaction Step One
Name
Name
Yield
70%
Identifiers
|
REACTION_CXSMILES
|
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH2:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[O:7][CH2:6]2.S(=O)(=O)(O)[O-].[K+].[OH-].[Na+]>ClCCl.S([O-])([O-])(=O)=O.[Ni+2]>[CH3:23][N:22]([CH2:21][CH2:20][CH2:19][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)[O:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]#[N:1])[CH:11]=[CH:10][C:9]1=2)[CH3:24] |f:1.2,3.4,6.7|
|
Inputs
Step One
|
Name
|
5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran
|
|
Quantity
|
0.5 g
|
|
Type
|
reactant
|
|
Smiles
|
NCC=1C=C2COC(C2=CC1)(C1=CC=C(C=C1)F)CCCN(C)C
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
S([O-])(O)(=O)=O.[K+]
|
|
Name
|
|
|
Quantity
|
19 mL
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
|
Name
|
|
|
Quantity
|
10 mL
|
|
Type
|
solvent
|
|
Smiles
|
ClCCl
|
Step Two
|
Name
|
|
|
Quantity
|
1.5 mL
|
|
Type
|
catalyst
|
|
Smiles
|
S(=O)(=O)([O-])[O-].[Ni+2]
|
Conditions
Stirring
|
Type
|
CUSTOM
|
|
Details
|
The mixture was stirred vigorously for 4 days
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was then filtered through celite
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The filtrate was partitioned between aqueous sulfuric acid (2 M) and toluene
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The aqueous layer was separated
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the pH of the mixture was adjusted to >9 by the addition of aqueous ammonia solution (25% w/v)
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
The solution was extracted with toluene
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
this latter toluene extract
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
was dried over magnesium sulfate
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated
|
Outcomes
Product
Details
Reaction Time |
4 d |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(C)CCCC1(C=2C=CC(=CC2CO1)C#N)C=3C=CC(=CC3)F
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 0.35 g | |
| YIELD: PERCENTYIELD | 70% |
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
US06660873B2
Procedure details
To a stirred solution of 5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran (0.5 g, 1.5 mmol) in dichloromethane (10 mL) was added an aqueous solution of potassium bisulfate and sodium hydroxide (19 mL; 0.2 M in K2S2O8, 3.8 mmol; 0.4 M in NaOH, 7.6 mmol), followed by an aqueous solution of nickel sulfate (1.5 mL, 40 mM, 61 μmol). The mixture was stirred vigorously for 4 days, and was then filtered through celite. The filtrate was partitioned between aqueous sulfuric acid (2 M) and toluene. The aqueous layer was separated, and the pH of the mixture was adjusted to >9 by the addition of aqueous ammonia solution (25% w/v). The solution was extracted with toluene, and this latter toluene extract was dried over magnesium sulfate and evaporated to give the free base of citalopram as a very pale yellow oil (0.35 g, 70%).
Name
5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran
Quantity
0.5 g
Type
reactant
Reaction Step One
Name
Name
Yield
70%
Identifiers
|
REACTION_CXSMILES
|
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH2:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[O:7][CH2:6]2.S(=O)(=O)(O)[O-].[K+].[OH-].[Na+]>ClCCl.S([O-])([O-])(=O)=O.[Ni+2]>[CH3:23][N:22]([CH2:21][CH2:20][CH2:19][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)[O:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]#[N:1])[CH:11]=[CH:10][C:9]1=2)[CH3:24] |f:1.2,3.4,6.7|
|
Inputs
Step One
|
Name
|
5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran
|
|
Quantity
|
0.5 g
|
|
Type
|
reactant
|
|
Smiles
|
NCC=1C=C2COC(C2=CC1)(C1=CC=C(C=C1)F)CCCN(C)C
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
S([O-])(O)(=O)=O.[K+]
|
|
Name
|
|
|
Quantity
|
19 mL
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
|
Name
|
|
|
Quantity
|
10 mL
|
|
Type
|
solvent
|
|
Smiles
|
ClCCl
|
Step Two
|
Name
|
|
|
Quantity
|
1.5 mL
|
|
Type
|
catalyst
|
|
Smiles
|
S(=O)(=O)([O-])[O-].[Ni+2]
|
Conditions
Stirring
|
Type
|
CUSTOM
|
|
Details
|
The mixture was stirred vigorously for 4 days
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was then filtered through celite
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The filtrate was partitioned between aqueous sulfuric acid (2 M) and toluene
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The aqueous layer was separated
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the pH of the mixture was adjusted to >9 by the addition of aqueous ammonia solution (25% w/v)
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
The solution was extracted with toluene
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
this latter toluene extract
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
was dried over magnesium sulfate
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated
|
Outcomes
Product
Details
Reaction Time |
4 d |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(C)CCCC1(C=2C=CC(=CC2CO1)C#N)C=3C=CC(=CC3)F
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 0.35 g | |
| YIELD: PERCENTYIELD | 70% |
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
US06660873B2
Procedure details
To a stirred solution of 5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran (0.5 g, 1.5 mmol) in dichloromethane (10 mL) was added an aqueous solution of potassium bisulfate and sodium hydroxide (19 mL; 0.2 M in K2S2O8, 3.8 mmol; 0.4 M in NaOH, 7.6 mmol), followed by an aqueous solution of nickel sulfate (1.5 mL, 40 mM, 61 μmol). The mixture was stirred vigorously for 4 days, and was then filtered through celite. The filtrate was partitioned between aqueous sulfuric acid (2 M) and toluene. The aqueous layer was separated, and the pH of the mixture was adjusted to >9 by the addition of aqueous ammonia solution (25% w/v). The solution was extracted with toluene, and this latter toluene extract was dried over magnesium sulfate and evaporated to give the free base of citalopram as a very pale yellow oil (0.35 g, 70%).
Name
5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran
Quantity
0.5 g
Type
reactant
Reaction Step One
Name
Name
Yield
70%
Identifiers
|
REACTION_CXSMILES
|
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8]([CH2:19][CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[O:7][CH2:6]2.S(=O)(=O)(O)[O-].[K+].[OH-].[Na+]>ClCCl.S([O-])([O-])(=O)=O.[Ni+2]>[CH3:23][N:22]([CH2:21][CH2:20][CH2:19][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)[O:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]#[N:1])[CH:11]=[CH:10][C:9]1=2)[CH3:24] |f:1.2,3.4,6.7|
|
Inputs
Step One
|
Name
|
5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran
|
|
Quantity
|
0.5 g
|
|
Type
|
reactant
|
|
Smiles
|
NCC=1C=C2COC(C2=CC1)(C1=CC=C(C=C1)F)CCCN(C)C
|
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
S([O-])(O)(=O)=O.[K+]
|
|
Name
|
|
|
Quantity
|
19 mL
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
|
Name
|
|
|
Quantity
|
10 mL
|
|
Type
|
solvent
|
|
Smiles
|
ClCCl
|
Step Two
|
Name
|
|
|
Quantity
|
1.5 mL
|
|
Type
|
catalyst
|
|
Smiles
|
S(=O)(=O)([O-])[O-].[Ni+2]
|
Conditions
Stirring
|
Type
|
CUSTOM
|
|
Details
|
The mixture was stirred vigorously for 4 days
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
FILTRATION
|
Type
|
FILTRATION
|
|
Details
|
was then filtered through celite
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The filtrate was partitioned between aqueous sulfuric acid (2 M) and toluene
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The aqueous layer was separated
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
the pH of the mixture was adjusted to >9 by the addition of aqueous ammonia solution (25% w/v)
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
The solution was extracted with toluene
|
EXTRACTION
|
Type
|
EXTRACTION
|
|
Details
|
this latter toluene extract
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
was dried over magnesium sulfate
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated
|
Outcomes
Product
Details
Reaction Time |
4 d |
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CN(C)CCCC1(C=2C=CC(=CC2CO1)C#N)C=3C=CC(=CC3)F
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
Measurements
| Type | Value | Analysis |
|---|---|---|
| AMOUNT: MASS | 0.35 g | |
| YIELD: PERCENTYIELD | 70% |
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. |
