Diethyl Malonate → 3-[4-(4-Chlorophenyl)-2-methyl-1,3-oxazol-5-yl]propanoic acid

HRID 1982433Notes

Reaction equation

HRID 1982433 reaction equation
[H-].[Na+].C(OCC)(=O)[CH2:4][C:5]([O:7]CC)=[O:6].Br[CH2:15][C:16]1[O:20][C:19]([CH3:21])=[N:18][C:17]=1[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1>CN(C)C=O.O>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C:17]2[N:18]=[C:19]([CH3:21])[O:20][C:16]=2[CH2:15][CH2:4][C:5]([OH:7])=[O:6])=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 132932935-(Bromomethyl)-4-(4-chlorophenyl)-2-methyl-1,3-oxazole

Product 1

HCID 132932823-[4-(4-Chlorophenyl)-2-methyl-1,3-oxazol-5-yl]propanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

60% Sodium hydride in oil (0.6 g) was added portionwise to a solution of diethyl malonate (4.8 g) in N,N-dimethylformamide (50 ml). The mixture was stirred for 10 minutes and a solution of 5-bromomethyl-4-(4-chlorophenyl)-2-methyloxazole (4.30 g) in N,N-dimethylformamide (20 ml) was added dropwise under ice-cooling. The mixture was stirred under ice-cooling for 30 minutes, diluted with water 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. The residue was dissolved in ethanol (30 ml), 2N sodium hydroxide (50 ml) was added, and the mixture was refluxed for 30 minutes, concentrated and washed with ethyl ether. The aqueous layer was acidified with hydrochloric acid and the precipitate was taken up 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 dissolved in pyridine (30 ml). The solution was refluxed with stirring for an hour and the pyridine was distilled off. To the residue was added water and the mixture was adjusted to pH 2 with hydrochloric acid. The resulting crystalline precipitate was collected by filtration to give 4-(4-chlorophenyl)-2-methyloxazole-5-propionic acid, yield 2.50 g (62.8%). Recrystallization from ethanol gave needles, yield 1.85 g (46.5%), m.p. 211°-212° C.

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred under ice-
  3. temperaturecooling for 30 minutes
  4. extractionextracted with ethyl ether
  5. washThe ethyl ether layer was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was then distilled off
  8. dissolutionThe residue was dissolved in ethanol (30 ml)
  9. addition2N sodium hydroxide (50 ml) was added
  10. temperaturethe mixture was refluxed for 30 minutes
  11. concentrationconcentrated
  12. washwashed with ethyl ether
  13. washThe ethyl ether layer was washed with water
  14. dry with materialdried over anhydrous magnesium sulfate
  15. distillationThe solvent was distilled off
  16. dissolutionthe residue was dissolved in pyridine (30 ml)
  17. temperatureThe solution was refluxed
  18. stirringwith stirring for an hour
  19. distillationthe pyridine was distilled off
  20. additionTo the residue was added water
  21. filtrationThe resulting crystalline precipitate was collected by filtration

Sources & evidence

ORD record
ord-5e5839e2465a43c8a5fde3f088a7b822
Source dataset
uspto-grants-1986_06
Patent number
US04596816

Reaction notes

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