2-Bromobenzoic acid → HCID 12249440, compound

HRID 1920731Notes

Reaction equation

HRID 1920731 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:11]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:12][C:13]([CH3:15])=[O:14].O1CCOCC1>[Cu]Br>[CH2:18]([O:17][C:11]([CH:12]([C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5])[C:13](=[O:14])[CH3:15])=[O:16])[CH3:19]

Participants

5

Reactant 3

HCID 69402-Bromobenzoic acidHCID 8868Ethyl AcetoacetateHCID 312751,4-Dioxane

Product 1

HCID 12249440HCID 12249440, compound

Reagents, catalysts & solvents 1

HCID 24593copper(I) bromideCatalyst

Procedure

To a cold (ice/water bath) stirred mixture of 2-bromobenzoic acid (20.1 g, 0.1 mol) and ethyl acetoacetate (13.01 g, 0.1 mol) in 1,4-dioxane (200 ml) sodium hydride (8 g, 0.2 mol, 60% dispersion in mineral oil) was added in small portions. After addition the cold bath was removed and the reaction mixture was allowed to stir at ambient temperature for 10 min. Copper (I) bromide (15.2 g, 0.106 mol) was added in portions and the obtained mixture was heated at reflux for 1 h. It was allowed to cool and stirred overnight at ambient temperature. The obtained green suspension was quenched with ethyl acetate (200 ml) and ice (300 g) and acidified with concentrated HCl (50 ml). The organic phase was washed with aq. 2 M HCl (2×100 ml) and brine, dried (Na2SO4) and evaporated in vacuo. The remaining mineral oil was removed by decantation after shaking with heptane (3×100 ml) and evaporation. Yield ca. 20 g, pale-yellow oil. The crude product was used in the next step without further purification. LC-MS (m/z) 205 ([M−CO2]+); tR=0.91. 1H NMR (500 MHz, DMSO-d6): mixture of at least 3 tautomers.

Workup

  1. additionwas added in small portions
  2. additionAfter addition the cold bath
  3. customwas removed
  4. temperaturethe obtained mixture was heated
  5. temperatureat reflux for 1 h
  6. temperatureto cool
  7. stirringstirred overnight at ambient temperature
  8. customThe obtained green suspension was quenched with ethyl acetate (200 ml) and ice (300 g)
  9. washThe organic phase was washed with aq. 2 M HCl (2×100 ml) and brine
  10. dry with materialdried (Na2SO4)
  11. customevaporated in vacuo
  12. customThe remaining mineral oil was removed by decantation
  13. stirringafter shaking with heptane (3×100 ml) and evaporation
  14. customThe crude product was used in the next step without further purification
  15. addition1H NMR (500 MHz, DMSO-d6): mixture of at least 3 tautomers

Sources & evidence

ORD record
ord-4ccd1037e7174769ac76dee65902d6dd
Source dataset
uspto-grants-2012_05
Patent number
US08173639B2

Reaction notes

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