Hydrochloric Acid → 3-(5-Methyl-2-phenyl-4-oxazolyl)propionic acid

HRID 1294178Notes

Reaction equation

HRID 1294178 reaction equation
C(OCC)(=O)[CH2:2][C:3]([O:5]CC)=[O:4].[H-].[Na+].Cl[CH2:15][C:16]1[N:17]=[C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:19][C:20]=1[CH3:21].Cl>O1CCCC1.C(O)(=O)C.O>[CH3:21][C:20]1[O:19][C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:17][C:16]=1[CH2:15][CH2:2][C:3]([OH:5])=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 97942894-(Chloromethyl)-5-methyl-2-phenyl-1,3-oxazole

Product 1

HCID 120932643-(5-Methyl-2-phenyl-4-oxazolyl)propionic acidYield 40.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of diethyl malonate (115.8 g) and tetrahydrofuran (300 mL) was added sodium hydride (60%, oil, 24.12 g) under ice-cooling. After stirring the mixture at room temperature for 30 min., a solution (100 mL) of 4-chloromethyl-5-methyl-2-phenyloxazole (50.0 g) in tetrahydrofuran was added to the reaction mixture under ice-cooling, and the mixture was heated under reflux for 1 hr. Water was added to the reaction mixture, and the mixture was concentrated. Ethyl acetate was added to the residue and the mixture was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give an oil. A mixture of this oil, 6N hydrochloric acid (300 mL) and acetic acid (150 ml) was heated under reflux for 20 hrs. The reaction mixture was concentrated, and ethyl acetate was added to the residue. The mixture was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give crystals (22.4 g, 40%) of 3-(5-methyl-2-phenyl-4-oxazolyl)propionic acid from a fraction eluted with ethyl acetate-hexane (1:4, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 124-125° C.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 1 hr
  5. concentrationthe mixture was concentrated
  6. additionEthyl acetate was added to the residue
  7. washthe mixture was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customto give an oil
  11. temperaturewas heated
  12. temperatureunder reflux for 20 hrs
  13. concentrationThe reaction mixture was concentrated
  14. additionethyl acetate was added to the residue
  15. washThe mixture was washed with saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-f496a0060b614f90a47f69d41801fbba
Source dataset
uspto-grants-2007_07
Patent number
US07238716B2

Reaction notes

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