Hydrochloric Acid → 3-[3-(4-Chlorophenyl)-5-methyl-4-isoxazolyl]propionic acid

HRID 1794454Notes

Reaction equation

HRID 1794454 reaction equation
Cl[CH2:2][C:3]1[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[N:5][O:6][C:7]=1[CH3:8].C(OCC)(=O)[CH2:17][C:18]([O:20]CC)=[O:19].[H-].[Na+].Cl>O1CCCC1>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([C:4]2[C:3]([CH2:2][CH2:17][C:18]([OH:20])=[O:19])=[C:7]([CH3:8])[O:6][N:5]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 222210554-(Chloromethyl)-3-(4-chlorophenyl)-5-methylisoxazole

Product 1

HCID 222212523-[3-(4-Chlorophenyl)-5-methyl-4-isoxazolyl]propionic acidYield 90.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Chloromethyl-3-(4-chlorophenyl)-5-methylisoxazole (1.21 g) was dissolved in tetrahydrofuran (50 ml) and added to a mixture of diethyl malonate (1.20 g), sodium hydride (60%, oil, 0.21 g) and tetrahydrofuran (20 ml) at 0° C. The mixture was stirred at 0° C. for 1 hr and then at room temperature overnight. The reaction mixture was acidified with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and a colorless oil was obtained from a fraction eluted with ethyl acetate-hexane (1:3, volume ratio). A mixture of the obtained colorless oil, 6N hydrochloric acid (30 ml) and acetic acid (30 ml) was refluxed for 5 hr. The reaction mixture was concentrated, and water was added to the residue. The obtained colorless crystals were filtrated to give 3-[3-(4-chlorophenyl)-5-methyl-4-isoxazolyl]propionic acid (1.20 g, yield 90%). The crystals were recrystallized from ethanol. melting point: 187–188° C.

Workup

  1. customat room temperature
  2. customovernight
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customa colorless oil was obtained from a fraction
  8. washeluted with ethyl acetate-hexane (1:3, volume ratio)
  9. additionA mixture of the obtained colorless oil, 6N hydrochloric acid (30 ml) and acetic acid (30 ml)
  10. temperaturewas refluxed for 5 hr
  11. concentrationThe reaction mixture was concentrated
  12. additionwater was added to the residue
  13. filtrationThe obtained colorless crystals were filtrated

Sources & evidence

ORD record
ord-6fc52140ceda4303be1751d53bcfa2cd
Source dataset
uspto-grants-2006_04
Patent number
US07022725B2

Reaction notes

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