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

HRID 1715197Notes

Reaction equation

HRID 1715197 reaction equation
C([O:3][C:4](=[O:10])[CH:5](Cl)[C:6]([CH3:8])=O)C.[CH:11]([NH2:13])=[O:12].[OH-].[Na+].Cl>CCOC(C)=O>[CH3:8][C:6]1[N:13]=[CH:11][O:12][C:5]=1[C:4]([OH:3])=[O:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 713FormamideHCID 11858Ethyl 2-chloroacetoacetateHCID 14798Sodium Hydroxide

Product 1

HCID 2923114-Methyl-1,3-oxazole-5-carboxylic acidYield 64.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
120 °C

Procedure

Ethyl-2-chloroacetoacetate (1 wt; 1 eq., 1000 g) was aged with formamide (0.68 vol; ca. 2.8 eq.) and the resulting solution was heated to 120° C. After 5 hours the mixture was allowed to cool to room temperature and allowed to age under nitrogen over night. The mixture was treated with NaOH (3 M, 6 vol, reaction moderately exothermic) and stirred at room temperature for 4 hours. Ethyl acetate (6 vol) was added and the phases allowed to separae. The organic layer was discarded while the aqueous was acidified with conc. (32%) aqueous HCl to pH 2 (ca. 2.0 vol). A precipitate started to form. The suspension was treated with AcOEt (8 vol) and vigorously stirred until the bulk of the precipitate had dissolved. The aqueous phase was further extracted with AcOEt twice (6 vol each) and the combined organic layers distilled to low volume (again a suspension was observed at low volume). Fresh AcOEt (8 vol) was added and the mixture evaporated to dryness. The collected solid was placed in the oven at 40° C. over night under reduced pressure to give 4-methyl-1,3-oxazole-5-carboxylic acid (498 g, 64.5%).

Workup

  1. temperatureto cool to room temperature
  2. waitallowed to age under nitrogen over night
  3. custom3 M, 6 vol, reaction moderately exothermic) and
  4. customto form
  5. stirringvigorously stirred until the bulk of the precipitate
  6. dissolutionhad dissolved
  7. extractionThe aqueous phase was further extracted with AcOEt twice (6 vol each) and the combined organic layers
  8. distillationdistilled to low volume (again a suspension
  9. additionFresh AcOEt (8 vol) was added
  10. customthe mixture evaporated to dryness
  11. waitThe collected solid was placed in the oven at 40° C. over night under reduced pressure

Sources & evidence

ORD record
ord-47497b7d47fd4aeb86a98501d76b2637
Source dataset
uspto-grants-2010_09
Patent number
US07799815B2

Reaction notes

Loading…