Sodium hydride → Methyl 2-[(2'-cyano-3,5-difluorobiphenyl-4-yl)methyl]-3-oxoheptanoate
Reaction equation
[O:1]=[C:2]([CH2:8][CH2:9][CH2:10][CH3:11])[CH2:3][C:4]([O:6][CH3:7])=[O:5].[H-].[Na+].Br[CH2:15][C:16]1[C:21]([F:22])=[CH:20][C:19]([C:23]2[C:24]([C:29]#[N:30])=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:18][C:17]=1[F:31].[Cl-].[NH4+]>O1CCCC1.O>[C:29]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:19]1[CH:18]=[C:17]([F:31])[C:16]([CH2:15][CH:3]([C:2](=[O:1])[CH2:8][CH2:9][CH2:10][CH3:11])[C:4]([O:6][CH3:7])=[O:5])=[C:21]([F:22])[CH:20]=1)#[N:30]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of methyl 3-oxoheptanoate (6.82 g) in tetrahydrofuran (75 mL) was added 60% sodium hydride (1.29 g), and the mixture was stirred for 1 hr. A solution of 4′-(bromomethyl)-3′,5′-difluorobiphenyl-2-carbonitrile (6.65 g) in tetrahydrofuran (25 mL), and the mixture was stirred for 15 hr. Ammonium chloride and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow viscous substance (7.93 g, 100%).
Workup
- extractionthe mixture was extracted with ethyl acetate
- washThe organic layer was washed with saturated brine
- dry with materialdried over anhydrous magnesium sulfate
- customthe solvent was evaporated
- customThe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-bcf0fc4ed15d4289814bb681e868acf5
- Source dataset
- uspto-grants-2011_08
- Patent number
- US07998968B2
Reaction notes
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