Sulfuric Acid → 2-Tert-butyl-5-methyl-4-oxazoleacetic acid

HRID 746033Notes

Reaction equation

HRID 746033 reaction equation
O=[C:2]([CH3:16])[CH:3]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][C:5]([O:7]C)=[O:6].S(=O)(=O)(O)O>C(OC(=O)C)(=O)C>[C:11]([C:10]1[O:15][C:2]([CH3:16])=[C:3]([CH2:4][C:5]([OH:7])=[O:6])[N:9]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 13282913Methyl 4-oxo-3-pivaloylaminovalerate

Product 1

HCID 132829732-Tert-butyl-5-methyl-4-oxazoleacetic acid

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 4-oxo-3-pivaloylaminovalerate was dissolved in acetic anhydride (15 ml), and concentrated sulfuric acid (1.2 ml) was added dropwise with stirring. The mixture was allowed to stand at room temperature for 20 minutes and heated at 80° C. for 5 minutes. The acetic anhydride was distilled off under reduced pressure and the residue was poured into 50 ml of ice water. The mixture was neutralized with potassium carbonate and extracted with ethyl ether. The ethyl ether layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was then distilled off and the oily residue (2.5 g) was stirred in a mixture of ethanol (13 ml) and 2N sodium hydroxide (13 ml) at room temperature for 30 minutes. The reaction mixture was diluted with water, adjusted to pH 2 with hydrochloric acid and extracted with ethyl ether. The ethyl ether layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was treated with hexane to give 2-tert-butyl-5-methyl-4-oxazoleacetic acid as crystals; yield 1.50 g (60.2%). Recrystallization from isopropyl ether gave colorless prisms melting at 121°-122° C.

Workup

  1. distillationThe acetic anhydride was distilled off under reduced pressure
  2. additionthe residue was poured into 50 ml of ice water
  3. extractionextracted with ethyl ether
  4. washThe ethyl ether layer was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationThe solvent was then distilled off
  7. stirringthe oily residue (2.5 g) was stirred in a mixture of ethanol (13 ml) and 2N sodium hydroxide (13 ml) at room temperature for 30 minutes
  8. additionThe reaction mixture was diluted with water
  9. extractionextracted with ethyl ether
  10. washThe ethyl ether layer was washed with water
  11. dry with materialdried over anhydrous magnesium sulfate
  12. distillationThe solvent was distilled off
  13. additionthe residue was treated with hexane

Sources & evidence

ORD record
ord-c42d34f2d8fe4551b10f11b4b6fe9f21
Source dataset
uspto-grants-1986_07
Patent number
US04602027

Reaction notes

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