Ethyl 2,4-dioxovalerate → 3-Methylisoxazole-5-carboxylic acid

HRID 864754Notes

Reaction equation

HRID 864754 reaction equation
[O:1]=[C:2]([CH2:8][C:9](=O)[CH3:10])[C:3]([O:5]CC)=[O:4].Cl.[NH2:13]O>Cl>[CH3:10][C:9]1[CH:8]=[C:2]([C:3]([OH:5])=[O:4])[O:1][N:13]=1

Participants

4

Reactant 2

HCID 69208Ethyl 2,4-dioxovalerateHCID 443297Hydroxyamine hydrochloride

Product 1

HCID 8530853-Methylisoxazole-5-carboxylic acidYield 58.7%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

Concentrated HCl (450 ml) was added to ethyl 2,4-dioxovalerate ( 177.8 g, 1.1 mol ) followed by hydroxylamine hydrochloride (103.7 g, 1.68 mol). The reaction mixture was stirred for 7 hours, then allowed to stand for 60 hours. The solvent was removed in vacuo and the residue was chilled on ice. A solid formed which was collected by filtration and washed with cold water. The solid was dissolved in THF (11), the solution was filtered and the solvent was removed in vacuo. The residue was slurried with ethyl acetate (200 ml) and the solid collected by filtration. Concentration of filtrate to approximately 30 ml afforded a second crop of the product. The two crops were combined and recrystallized from methanol to afford 82.1 g (58%) of 3-methylisoxazole-5-carboxylic acid, m.p. 209°-211° C.

Workup

  1. waitto stand for 60 hours
  2. customThe solvent was removed in vacuo
  3. temperaturethe residue was chilled on ice
  4. customA solid formed which
  5. filtrationwas collected by filtration
  6. washwashed with cold water
  7. dissolutionThe solid was dissolved in THF (11)
  8. filtrationthe solution was filtered
  9. customthe solvent was removed in vacuo
  10. filtrationthe solid collected by filtration
  11. customConcentration of filtrate to approximately 30 ml afforded a second crop of the product
  12. customrecrystallized from methanol

Sources & evidence

ORD record
ord-6efcb06286f4457f97b07aa2bdcf016a
Source dataset
uspto-grants-1996_10
Patent number
US05563163

Reaction notes

Loading…