tert-Butyl bromoacetate → tert-Butyl 4-(2,6-difluorophenyl)-4-oxobutyrate

HRID 2276662Notes

Reaction equation

HRID 2276662 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

HCID 79177tert-Butyl bromoacetateHCID 836431-(2,6-Difluorophenyl)ethan-1-oneHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 21964547tert-Butyl 4-(2,6-difluorophenyl)-4-oxobutyrate

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

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 stifling 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

  1. washwashed with water and brine
  2. extractionThe aqueous layer was extracted one more time with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography on a silica gel column (hex: ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-2b6e343bb37a4965b6c7e2871706d3bc
Source dataset
uspto-grants-2015_09
Patent number
US09133073B2

Reaction notes

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