Ammonia → HCID 19973071, compound

HRID 1451949Notes

Reaction equation

HRID 1451949 reaction equation
Cl[CH2:2][C:3]([OH:18])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:4]([F:11])([F:10])[C:5](OCC)=[O:6].[NH3:19].Cl.[NH:21]1[CH:25]=[N:24][CH:23]=[N:22]1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.CN(C)C=O.O.C(OCC)(=O)C>[F:10][C:4]([F:11])([C:3]([OH:18])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2][N:21]1[CH:25]=[N:24][CH:23]=[N:22]1)[C:5]([NH2:19])=[O:6]

Participants

10

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric Acid2×HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 19973079HCID 19973079, compound

Product 1

HCID 19973071HCID 19973071, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

In 5 ml of ethanol was dissolved 1.0 g of ethyl 4-chloro-2,2-difluoro-3-hydroxy-3-phenylbutyrate. To the resulting solution was added 0.98 ml of a concentrated aqueous ammonia. The solution was subjected to reaction at 25°-30° C. for 3 hours. The solvent was removed by distillation under reduced pressure. To the residue obtained were added 20 ml of ethyl acetate and 20 ml of water. The resulting solution was adjusted to pH 1.0 with 6N hydrochloric acid. 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 obtained was dissolved in 10 ml of N,N-dimethylformamide. To the solution were added 0.5 g of 1,2,4-triazole and 1.0 g of anhydrous potassium carbonate. The resulting mixture was subjected to reaction at 70° C. for 10 hours. Then, the solvent was removed by distillation under reduced pressure. To the residue obtained were added 20 ml of ethyl acetate and 20 ml of water. The resulting solution was adjusted to pH 1.0 with 6N hydrochloric acid. 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=50/1) to obtain 0.30 g of 2,2-difluoro-3-hydroxy-3-phenyl-4-(1H-1,2,4-triazol-1yl)butanamide.

Workup

  1. customThe solution was subjected to reaction at 25°-30° C. for 3 hours
  2. customThe solvent was removed by distillation under reduced pressure
  3. customTo the residue obtained
  4. customThe organic layer was separated
  5. washwashed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThereafter, the solvent was removed by distillation under reduced pressure
  8. customThe residue obtained
  9. customThe resulting mixture was subjected to reaction at 70° C. for 10 hours
  10. customThen, the solvent was removed by distillation under reduced pressure
  11. customTo the residue obtained
  12. customThe organic layer was separated
  13. washwashed with a saturated aqueous sodium chloride solution
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customThereafter, the solvent was removed by distillation under reduced pressure
  16. customThe residue thus obtained
  17. customwas purified by a column chromatography (eluant:chloroform/methanol=50/1)

Sources & evidence

ORD record
ord-45489c922ee04f51a2c18583f4f5c49e
Source dataset
uspto-grants-1997_02
Patent number
US05605921

Reaction notes

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