Hydrochloric Acid → 4-Methyl-1,3-oxazole-5-carboxylic acid

HRID 563940

Reaction equation

HRID 563940 reaction equation
C(OC(=O)C(Cl)C(=O)C)C.C([O-])=O.[NH4+].C([O-])([O-])=O.[Na+].[Na+].C([O:23][C:24]([C:26]1[O:30][CH:29]=[N:28][C:27]=1[CH3:31])=[O:25])C.Cl>C(O)=O.O.[OH-].[Na+]>[CH3:31][C:27]1[N:28]=[CH:29][O:30][C:26]=1[C:24]([OH:25])=[O:23]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11858Ethyl 2-chloroacetoacetateHCID 88558Ethyl 4-methyloxazole-5-carboxylateHCID 2723923Ammonium formate

Product 1

HCID 2923114-Methyl-1,3-oxazole-5-carboxylic acid

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 40.0 grams (0.243 mol, 1.0 eq) of 2-Chloro-3-oxo-butyric acid ethyl ester in 240 mL formic acid (99%) was stirred at room temperature in a 500 mL round bottom flask equipped with a H2O condenser. To this solution was added 80.0 grams (1.27 mmol, 5.2 eq) of ammonium formate. The solution was then heated to reflux for five hours. After cooling to room temperature, the solution was diluted with water (1 L) and neutralized with Na2CO3. The aqueous solution was then extracted three times with Et2O and the combined organic fractions were dried over MgSO4. After concentration, vacuum distillation (˜10 mmHg, b.p. 53° C.-61° C.) gave a mixture of starting material and 4-Methyl-oxazole-5-carboxylic acid ethyl ester as a colorless oil (21.7 grams). This mixture was dissolved in 100 mL of aqueous sodium hydroxide (2 N) and refluxed for 1 minute. The reaction was then poured onto ice and acidified with concentrated HCl and the known (Sen & Sengupta (1985) Ind. J. Chem. Section B: Org. Chem. Including Med. Chem. 24B(5):535-8) free acid precipitated as a white solid (6.04 grams, 20% overall yield) Mp: 241.4-242.6° C.

Workup

  1. customequipped with a H2O condenser
  2. temperatureThe solution was then heated
  3. temperatureto reflux for five hours
  4. extractionThe aqueous solution was then extracted three times with Et2O
  5. dry with materialthe combined organic fractions were dried over MgSO4
  6. concentrationAfter concentration, vacuum distillation (˜10 mmHg, b.p. 53° C.-61° C.)
  7. customgave
  8. temperaturerefluxed for 1 minute
  9. additionThe reaction was then poured onto ice
  10. custom535-8) free acid precipitated as a white solid (6.04 grams, 20% overall yield) Mp: 241.4-242.6° C.

Sources & evidence

ORD record
ord-e06c82575c51497491332e727a5182bc
Source dataset
uspto-grants-2011_11
Patent number
US08067583B2

Linked notes

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