Formic Acid → Ethyl oxazole-4-carboxylate

HRID 1096815Notes

Reaction equation

HRID 1096815 reaction equation
C(O)=O.C1N=CN([C:9]([N:11]2C=N[CH:13]=[CH:12]2)=[O:10])C=1.[N+](C[C:19]([O:21][CH2:22][CH3:23])=[O:20])#[C-].CCN(CC)CC>C1COCC1.O>[CH2:22]([O:21][C:19]([C:12]1[N:11]=[CH:9][O:10][CH:13]=1)=[O:20])[CH3:23]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 533707Ethyl isocyanoacetate

Product 1

HCID 2763217Ethyl oxazole-4-carboxylateYield 84.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a sol. of formic acid (8.62 mL, 228 mmol) in dry THF (200 mL) was added portionwise CDI (37.05 g, 228 mmol), whereas a gas evolution occurred. The mixture was stirred for 30 min, and a sol. of ethyl isocyanoacetate (25 mL, 228 mmol) in Et3N (60.5 mL, 434 mmol) was added to the reaction mixture. The mixture was stirred at rt for 1 h, then under reflux overnight. The reaction mixture was allowed to cool to rt. Water was added, and the mixture was extracted with Et2O (3×). The combined org. extracts were dried over MgSO4, filtered and concentrated. Purification of the residue by FC (EtOAc/heptane; 1:5 →1:3→1:1) yielded the title compound (27.2 g, 84%). LC-MS: tR=0.58, ES+: 142.07.

Workup

  1. stirringThe mixture was stirred at rt for 1 h
  2. temperatureunder reflux overnight
  3. extractionthe mixture was extracted with Et2O (3×)
  4. dry with materialextracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue by FC (EtOAc/heptane; 1:5 →1:3→1:1)

Sources & evidence

ORD record
ord-c4ab697913c64ba7a6e934c344a5e722
Source dataset
uspto-grants-2012_03
Patent number
US08138340B2

Reaction notes

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