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

HRID 1982434Notes

Reaction equation

HRID 1982434 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][CH:25]=[C:24]([Cl:28])[CH:23]=1>CN(C)C=O.O>[Cl:28][C:24]1[CH:23]=[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:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 233165925-(Bromomethyl)-4-(3-chlorophenyl)-2-methyl-1,3-oxazole

Product 1

HCID 132932843-[4-(3-Chlorophenyl)-2-methyl-1,3-oxazol-5-yl]propanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

60% Sodium hydride in oil (0.47 g) was added portionwise to a solution of diethyl malonate (3.4 g) in N,N-dimethylformamide (20 ml) and under ice-cooling a solution of 5-bromomethyl-4-(3-chlorophenyl)-2-methyloxazole (3 g) in N,N-dimethylformamide (10 ml) was added. 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 and the residue was dissolved in ethanol (20 ml), followed by addition of 2N sodium hydroxide (20 ml). The mixture was refluxed for 5 minutes, diluted with water and washed with ethyl ether. The aqueous layer was adjusted to pH 2 with hydrochloric acid and extracted with ethyl ether The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off and the oily residue (mostly, half-ester) was dissolved in pyridine (20 ml). The solution was refluxed for 2.5 hours. The pyridine was then distilled off and the residue [mostly, ethyl 4-(3-chlorophenyl)-2-methyloxazole-5-propionate] was dissolved in a mixture of ethanol (10 ml) and 2N sodium hydroxide (10 ml). The solution was refluxed for 5 minutes, diluted with water and acidified with hydrochloric acid to give crsytals of 4-(3-chlorophenyl)-2-methyloxazole-5-propionic acid, yield 1.6 g (56.7%), m.p. 159°-160° C.

Workup

  1. additionwas added
  2. temperaturecooling for 30 minutes
  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. dissolutionthe residue was dissolved in ethanol (20 ml)
  8. additionfollowed by addition of 2N sodium hydroxide (20 ml)
  9. temperatureThe mixture was refluxed for 5 minutes
  10. additiondiluted with water
  11. washwashed with ethyl ether
  12. extractionextracted with ethyl ether The extract
  13. washwas washed with water
  14. dry with materialdried over anhydrous magnesium sulfate
  15. distillationThe solvent was distilled off
  16. dissolutionthe oily residue (mostly, half-ester) was dissolved in pyridine (20 ml)
  17. temperatureThe solution was refluxed for 2.5 hours
  18. distillationThe pyridine was then distilled off
  19. dissolutionthe residue [mostly, ethyl 4-(3-chlorophenyl)-2-methyloxazole-5-propionate] was dissolved in a mixture of ethanol (10 ml) and 2N sodium hydroxide (10 ml)
  20. temperatureThe solution was refluxed for 5 minutes
  21. additiondiluted with water

Sources & evidence

ORD record
ord-eb189660b88c40189d9f16c4076eb5f9
Source dataset
uspto-grants-1986_06
Patent number
US04596816

Reaction notes

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