Hydrochloric Acid → HCID 22221003, compound

HRID 1794455Notes

Reaction equation

HRID 1794455 reaction equation
Cl[CH2:2][C:3]1[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=[N:5][O:6][C:7]=1[CH3:8].C(OCC)(=O)[CH2:20][C:21]([O:23]CC)=[O:22].[H-].[Na+].Cl>O1CCCC1>[CH3:8][C:7]1[O:6][N:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[C:3]=1[CH2:2][CH2:20][C:21]([OH:23])=[O:22]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 22220975HCID 22220975, compound

Product 1

HCID 22221003HCID 22221003, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-chloromethyl-5-methyl-3-(4-trifluoromethylphenyl)isoxazole (1.37 g) in tetrahydrofuran (50 ml) was 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-[5-methyl-3-(4-trifluoromethylphenyl)-4-isoxazolyl]propionic acid (1.25 g, yield 84%). The crystals were recrystallized from ethanol-hexane. melting point: 138–139° 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-794ab5aa12114d5c84e6d22eec0fb8f3
Source dataset
uspto-grants-2006_04
Patent number
US07022725B2

Reaction notes

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