Ethyl Acetate → HCID 9948882, compound

HRID 1451943Notes

Reaction equation

HRID 1451943 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:22])([CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1)[C:10]([F:15])([F:14])[C:11](O)=[O:12].O[N:24]1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.C(OCC)(=O)C>O1CCOCC1.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:22])([CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1)[C:10]([F:15])([F:14])[C:11]([NH2:24])=[O:12]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 19973070HCID 19973070, compound

Product 1

HCID 9948882HCID 9948882, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

In 20 ml of dioxane were dissolved 300 mg of 3-(2,4-difluorophenyl)-2,2-difluoro-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butyric acid and 110 mg of N-hydroxysuccinimide. To the resulting solution was added 200 mg of N,N'-dicyclohexylcarbodiimide. Then, the resulting mixture was subjected to reaction at 15°-25° C. for 3 hours. The reaction mixture was subjected to filtration to remove the insolubles, and 4.5 ml of a concentrated aqueous ammonia solution was added to the filtrate. The resulting mixture was subjected to reaction at 15°-25° C. for 20 hours. Then, the solvent was removed by distillation under reduced pressure. To the residue obtained were added 20 ml of ethyl acetate and 10 ml of water. The organic layer was separated, washed with a saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by a column chromatography (eluant: chloroform/methanol=10/1) to obtain 70 mg of 3-(2,4-difluorophenyl)-2,2-difluoro-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butanamide.

Workup

  1. customThen, the resulting mixture was subjected to reaction at 15°-25° C. for 3 hours
  2. filtrationThe reaction mixture was subjected to filtration
  3. customto remove the insolubles, and 4.5 ml of a concentrated aqueous ammonia solution
  4. additionwas added to the filtrate
  5. customThe resulting mixture was subjected to reaction at 15°-25° C. for 20 hours
  6. customThen, the solvent was removed by distillation under reduced pressure
  7. customTo the residue obtained
  8. customThe organic layer was separated
  9. washwashed with a saturated aqueous sodium chloride solution
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThereafter, the solvent was removed by distillation under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by a column chromatography (eluant: chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-b2af5162879b41178737a7870feb5c02
Source dataset
uspto-grants-1997_02
Patent number
US05605921

Reaction notes

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