Patent
US07186854B2
Procedure details
0.500 g of the epoxyamide (5A) was dissolved in a mixture of 40 ml of chloroform and 40 ml of water and 371 mg of sodium p-fluorobenzenesulfinate was added. Subsequently, 298 mg of tetrabutylammonium bromide was added. The reaction mixture was heated till reflux, while stirring vigorously. The reaction was monitored with HPLC. After 96 hours of reflux, the reaction mixture was cooled to room temperature. 20 ml of chloroform was added and the organic layer was washed with 3×50 ml of water, dried (Na2SO4) and evaporated to dryness. Yield: 860 mg. Purification of the crude product by column chromatography (Merck silica gel 60; eluent: heptane/ethyl acetate=1/1) afforded bicalutamide as white solid. Isolated yield: 380 mg (48%). 1H-NMR: confirmed the structure.
Name
sodium p-fluorobenzenesulfinate
Quantity
371 mg
Type
reactant
Reaction Step One
Name
Identifiers
|
REACTION_CXSMILES
|
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O-:29])=[O:28])=[CH:23][CH:22]=1.[Na+]>C(Cl)(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:12]([OH:13])([C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:5]=1)=[O:11])[CH2:14][S:27]([C:24]1[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=1)(=[O:29])=[O:28] |f:1.2,5.6|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0.5 g
|
|
Type
|
reactant
|
|
Smiles
|
C(#N)C1=C(C=C(C=C1)NC(=O)C1(OC1)C)C(F)(F)F
|
|
Name
|
sodium p-fluorobenzenesulfinate
|
|
Quantity
|
371 mg
|
|
Type
|
reactant
|
|
Smiles
|
FC1=CC=C(C=C1)S(=O)[O-].[Na+]
|
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Step Two
|
Name
|
|
|
Quantity
|
298 mg
|
|
Type
|
catalyst
|
|
Smiles
|
[Br-].C(CCC)[N+](CCCC)(CCCC)CCCC
|
Step Three
|
Name
|
|
|
Quantity
|
20 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
while stirring vigorously
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
was added
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The reaction mixture was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
till reflux
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After 96 hours of reflux
|
|
Duration
|
96 h
|
WASH
|
Type
|
WASH
|
|
Details
|
the organic layer was washed with 3×50 ml of water
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried (Na2SO4)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated to dryness
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Purification of the crude product by column chromatography (Merck silica gel 60; eluent: heptane/ethyl acetate=1/1)
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(CS(=O)(=O)C=1C=CC(=CC1)F)(C(=O)NC=2C=CC(=C(C2)C(F)(F)F)C#N)O
|
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
US07186854B2
Procedure details
0.500 g of the epoxyamide (5A) was dissolved in a mixture of 40 ml of chloroform and 40 ml of water and 371 mg of sodium p-fluorobenzenesulfinate was added. Subsequently, 298 mg of tetrabutylammonium bromide was added. The reaction mixture was heated till reflux, while stirring vigorously. The reaction was monitored with HPLC. After 96 hours of reflux, the reaction mixture was cooled to room temperature. 20 ml of chloroform was added and the organic layer was washed with 3×50 ml of water, dried (Na2SO4) and evaporated to dryness. Yield: 860 mg. Purification of the crude product by column chromatography (Merck silica gel 60; eluent: heptane/ethyl acetate=1/1) afforded bicalutamide as white solid. Isolated yield: 380 mg (48%). 1H-NMR: confirmed the structure.
Name
sodium p-fluorobenzenesulfinate
Quantity
371 mg
Type
reactant
Reaction Step One
Name
Identifiers
|
REACTION_CXSMILES
|
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O-:29])=[O:28])=[CH:23][CH:22]=1.[Na+]>C(Cl)(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:12]([OH:13])([C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:5]=1)=[O:11])[CH2:14][S:27]([C:24]1[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=1)(=[O:29])=[O:28] |f:1.2,5.6|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0.5 g
|
|
Type
|
reactant
|
|
Smiles
|
C(#N)C1=C(C=C(C=C1)NC(=O)C1(OC1)C)C(F)(F)F
|
|
Name
|
sodium p-fluorobenzenesulfinate
|
|
Quantity
|
371 mg
|
|
Type
|
reactant
|
|
Smiles
|
FC1=CC=C(C=C1)S(=O)[O-].[Na+]
|
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
|
Name
|
|
|
Quantity
|
40 mL
|
|
Type
|
solvent
|
|
Smiles
|
O
|
Step Two
|
Name
|
|
|
Quantity
|
298 mg
|
|
Type
|
catalyst
|
|
Smiles
|
[Br-].C(CCC)[N+](CCCC)(CCCC)CCCC
|
Step Three
|
Name
|
|
|
Quantity
|
20 mL
|
|
Type
|
solvent
|
|
Smiles
|
C(Cl)(Cl)Cl
|
Conditions
Temperature
|
Control Type
|
AMBIENT
|
Stirring
|
Type
|
CUSTOM
|
|
Details
|
while stirring vigorously
|
|
Rate
|
UNSPECIFIED
|
|
RPM
|
0
|
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
ADDITION
|
Type
|
ADDITION
|
|
Details
|
was added
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
The reaction mixture was heated
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
till reflux
|
TEMPERATURE
|
Type
|
TEMPERATURE
|
|
Details
|
After 96 hours of reflux
|
|
Duration
|
96 h
|
WASH
|
Type
|
WASH
|
|
Details
|
the organic layer was washed with 3×50 ml of water
|
DRY_WITH_MATERIAL
|
Type
|
DRY_WITH_MATERIAL
|
|
Details
|
dried (Na2SO4)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
evaporated to dryness
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Purification of the crude product by column chromatography (Merck silica gel 60; eluent: heptane/ethyl acetate=1/1)
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(CS(=O)(=O)C=1C=CC(=CC1)F)(C(=O)NC=2C=CC(=C(C2)C(F)(F)F)C#N)O
|
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. |
