Ethyl Acetoacetate → 2-Cyclopropanecarbonyl-3-oxo-butyric acid ethyl ester

HRID 1011874Notes

Reaction equation

HRID 1011874 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[CH2:5][C:6]([CH3:8])=[O:7])[CH3:2].C([Mg]Cl)(C)C.[CH:15]1([C:18](Cl)=[O:19])[CH2:17][CH2:16]1>C1COCC1.N1C=CN=C1>[CH2:1]([O:3][C:4](=[O:9])[CH:5]([C:18]([CH:15]1[CH2:17][CH2:16]1)=[O:19])[C:6](=[O:7])[CH3:8])[CH3:2]

Participants

6

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 77637Cyclopropanecarbonyl chlorideHCID 178418918HCID 178418918, compound

Product 1

HCID 669015882-Cyclopropanecarbonyl-3-oxo-butyric acid ethyl esterYield 71%

Reagents, catalysts & solvents 2

HCID 795ImidazoleCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethylacetoacetate (11.0 g, 85 mmol) in THF (20 ml) at 0° C. under argon atmosphere was added isopropylmagnesium chloride (42 ml, 2 M in THF, 85 mmol) dropwise. The reaction was stirred for 0.5 h. This solution was then transferred by cannula to a solution of cyclopropylcarbonylchloride (8.8 g, 85 mmol) and imidazole (0.3 g, 4 mmol) in THP (30 ml), also under argon at 0° C. The reaction was stirred for 2 h at 0° C. and 1 h at room temperature before the reaction was quenched by addition of 10% citric acid solution. The reaction was then extracted with EtOAc, dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc:n-heptane 5:95) afforded the title compound (11.9 g, 71%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.99-1.02 (2H, m), 1.22-1.24 (2H, m), 1.35 (3H, t, J=6 Hz), 2.32 (3H, s), 2.41-2.51 (1H, m), 4.30 (2H, q, J=6 Hz), 17.95 (1H, s).

Workup

  1. stirringThe reaction was stirred for 2 h at 0° C. and 1 h at room temperature before the reaction
  2. customwas quenched by addition of 10% citric acid solution
  3. extractionThe reaction was then extracted with EtOAc
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (EtOAc:n-heptane 5:95)

Sources & evidence

ORD record
ord-8bbf8cd106a54a449154f88006e13ed4
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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