Lithium diisopropylamide → tert-Butyl 4-[2-{3-cyano-4-fluoro-2-methylphenyl}-2-oxoethyl]-3-oxopiperazine-1-carboxylate
Reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:24][C:25]([C:27]1[C:28]([CH3:36])=[C:29]([C:32]([F:35])=[CH:33][CH:34]=1)[C:30]#[N:31])=[O:26]>C1COCC1>[C:30]([C:29]1[C:28]([CH3:36])=[C:27]([C:25](=[O:26])[CH2:24][N:7]2[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][C:2]2=[O:1])[CH:34]=[CH:33][C:32]=1[F:35])#[N:31]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a THF solution of tert-butyl 3-oxopiperazine-1-carboxylate (0.080 g, 0.43 mmol) was added Lithium diisopropylamide (0.20 mL, 0.39 mmol) drop wise at −78° C. After stirring for 15 min., a THF solution of 3-(bromoacetyl)-6-fluoro-2-methylbenzonitrile (0.10 g, 0.39 mmol) was added to the reaction mixture slowly. Analysis of the reaction mixture by LC indicated formation of the desired product. To the reaction mixture was sat. NH4Cl followed by extraction of the aqueous layer with EtOAc. The extractions were combined and washed with brine, dried with Na2SO4, and concentrated under reduced pressure to provide a residue which was then subjected for purification by silica gel column chromatography (10% MeOH in DCM) to provide the title product. LC/MS (IE, m/z): [M+1]+=376.
Sources & evidence
- ORD record
- ord-072534dbd3c24cb7aeeea6758e2a8572
- Source dataset
- uspto-grants-2015_04
- Patent number
- US08999990B2
Reaction notes
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