Ethyl bromoacetate → 4-(4-Methoxy-phenyl)-3-methyl-4-oxo-butyric acid ethyl ester

HRID 887042Notes

Reaction equation

HRID 887042 reaction equation
[CH3:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)=[O:4].C([N-]C(C)C)(C)C.[Li+].Br[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]>O1CCCC1>[CH2:26]([O:25][C:23](=[O:24])[CH2:22][CH:2]([CH3:1])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)=[O:4])[CH3:27]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 671444-PropanoylanisoleHCID 2724682Lithium diisopropylamide

Product 1

HCID 148665764-(4-Methoxy-phenyl)-3-methyl-4-oxo-butyric acid ethyl esterYield 125.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-methoxypropiophenone (24 g, 140 mmol) in tetrahydrofuran (220 mL) was cooled to 0° C. Lithium diisopropylamide, (2M solution in THF) (126 mL, 248 mmol) was added dropwise and warmed to rt for 30 min. The reaction was cooled again to 0° C. and ethyl bromoacetate (18 mL, 161 mmol) was added dropwise and warmed to rt for 30 min and then quenched with aqueous 1M HCl acid at 0° C. The aqueous layer was extracted twice with methylene chloride and the combined organics were washed with brine, dried (Na2SO4), filtered, and concentrated to give 4-(4-methoxyphenyl)-3-methyl-4-oxobutyric acid ethyl ester (44 g), MS m/z 205 (M−45)

Workup

  1. temperatureThe reaction was cooled again to 0° C.
  2. temperaturewarmed to rt for 30 min
  3. customquenched with aqueous 1M HCl acid at 0° C
  4. extractionThe aqueous layer was extracted twice with methylene chloride
  5. washthe combined organics were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6507ecadea2249a680cdc67b818c755d
Source dataset
uspto-grants-2012_08
Patent number
US08247414B2

Reaction notes

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