1-Bromo-2-methylpropane → 2-Isobutyl-3-ketoglutarate diethyl ester

HRID 1031245

Reaction equation

HRID 1031245 reaction equation
[O:1]=[C:2]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[O-]CC.[Mg+2].[O-]CC.Br[CH2:23][CH:24]([CH3:26])[CH3:25]>>[CH3:23][CH:24]([CH3:26])[CH2:25][CH:9]([C:2](=[O:1])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

4

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 66045Diethyl acetonedicarboxylateHCID 164963Magnesium ethanolate

Product 1

HCID 99926592-Isobutyl-3-ketoglutarate diethyl esterYield 62%

Procedure

Diethyl 3-oxopentanedioate (45.5 ml, 0.25 mol) was added to a suspension of magnesium ethoxide (prepared from magnesium turnings (9 g, 0.375 mol) and iodine (0.1 g) in dry ethanol (275 ml)), and the mixture was heated under reflux for 90 min. 1-Bromo-2-methylpropane (54 ml, 0.5 mol) was added, and the reaction was heated under reflux for 16 h. Further 1-bromo-2-methylpropane (27 ml, 0.25 mol) was added to the boiling mixture, and after 3 h the solvent was evaporated in vacuo. The residue was partitioned between 2 N hydrochloric acid and ether. After extracting the aqueous phase with ether, the combined organics were washed successively with water, 5% sodium bicarbonate, water and brine, then were dried (Na2SO4) and evaporated in vacuo. The residue was distilled to give the title compound as a colourless oil (40 g, 62%), bp 118°-120° C. (1 mmHg). δ (CDCl3): 0.9 (6H, d, J=6Hz), 1.25 (6H, t, J=7Hz), 1.4-1.9 (3H, m), 3.5 (2H, s), 3.7 (1H, d, J=9Hz) and 4.2 (4H, q, J=7Hz).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 90 min
  3. temperaturethe reaction was heated
  4. temperatureunder reflux for 16 h
  5. customafter 3 h the solvent was evaporated in vacuo
  6. customThe residue was partitioned between 2 N hydrochloric acid and ether
  7. extractionAfter extracting the aqueous phase with ether
  8. washthe combined organics were washed successively with water, 5% sodium bicarbonate, water and brine
  9. dry with materialwere dried (Na2SO4)
  10. customevaporated in vacuo
  11. distillationThe residue was distilled

Sources & evidence

ORD record
ord-9f409073cecb4cee984edb22c535e47b
Source dataset
uspto-grants-1992_04
Patent number
US05109000

Linked notes

Loading…