tert-Butyl bromoacetate → tert-Butyl 4-(2,6-difluorophenyl)-4-oxobutyrate
Reaction equation
[CH3:1][C:2]([C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[F:11])=[O:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>C1COCC1.CN1C(=O)N(C)CCC1.CCOC(C)=O>[F:11][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([F:10])[C:4]=1[C:2](=[O:3])[CH2:1][CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]Participants
7
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -60 °C
Procedure
To a stirred solution of 2,6-Difluoroacetophenone (5 g, 32 mmol) in dry THF (40 ml) and DMPU (8 ml) was added a solution of lithium bis(trimethylsilyl)amide (1.0M, 45 ml) at −60° C. under argon. After stirring for 10 minutes at −60° C., tert-Butyl bromoacetate (6.99 g, 35.8 mmol) was added rapidly. The reaction mixture was stirred for an additional 10 minutes and then warmed to room temperature for 4 hours. The crude mixture was taken in EtOAc and washed with water and brine. The aqueous layer was extracted one more time with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (hex: ethyl acetate, 2:1) to provide the title compound.
Workup
- stirringThe reaction mixture was stirred for an additional 10 minutes
- temperaturewarmed to room temperature for 4 hours
- washwashed with water and brine
- extractionThe aqueous layer was extracted one more time with EtOAc
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- custompurified by flash chromatography on a silica gel column (hex: ethyl acetate, 2:1)
Sources & evidence
- ORD record
- ord-f644e97702b84853a7afa87cee9c91cd
- Source dataset
- uspto-grants-2005_08
- Patent number
- US06924314B2
Reaction notes
Loading…