Sodium hydride → Methyl 2-[(2'-cyano-2-fluorobiphenyl-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[CH:21]=[CH:20][C:19]([C:22]2[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)=[C:18]([F:30])[CH:17]=1>O1CCCC1>[C:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:19]1[CH:20]=[CH:21][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])=[CH:17][C:18]=1[F:30])#[N:29]Participants
Procedure
A solution of methyl 3-oxoheptanoate (7 g) in tetrahydrofuran (30 mL) was added to a mixture of sodium hydride (1.2 g) and tetrahydrofuran (80 mL) at room temperature, and the mixture was stirred at room temperature for 30 min. And then, 4′-(bromomethyl)-2′-fluorobiphenyl-2-carbonitrile (5.3 g) was added to the reaction mixture, and the reaction mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated, the residue was extracted with 5% aqueous potassium hydrogensulfate solution and then with ethyl acetate, and the ethyl acetate layer was washed with saturated brine and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless oil (7.3 g, 90%).
Workup
- stirringthe reaction mixture was stirred at room temperature for 3 days
- concentrationThe reaction mixture was concentrated
- extractionthe residue was extracted with 5% aqueous potassium hydrogensulfate solution
- washwith ethyl acetate, and the ethyl acetate layer was washed with saturated brine
- concentrationconcentrated
- customThe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-c7ed19b1bc2d4276a5de3e2738e02d87
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08921379B2
Reaction notes
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