1H-1,2,4-Triazole → HCID 14706434, compound

HRID 368895Notes

Reaction equation

HRID 368895 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]1([O:21][CH2:20]1)[C@@H:17]([OH:19])[CH3:18]>CN(C)C=O>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]([OH:21])([C@@H:17]([OH:19])[CH3:18])[CH2:20][N:3]1[CH:7]=[N:6][CH:5]=[N:4]1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 10631861(1S)-[(2R)-(2,4-difluorophenyl)-2-oxiranyl]ethanol2×

Product 1

HCID 14706434HCID 14706434, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

To an ice cooled suspension of dry NaH (0.216 g, 0.009 mole) in N,N-dimethylformamide (10 ml), 1H-1,2,4-Triazole (0.691, 0.010 mole) was added in small portions under an atmosphere of nitrogen. The mixture was slowly brought to room temperature and a solution of compound 7a, (2S,3R)-3-(2,4-Difluorophenyl)-3,4-epoxy-2-butanol (1.0 g, 0.005 mole) in N,N-dimethylformamide (2 ml) was added. The resulting mixture was heated at 80° C. for 2 hours. The solvent was removed under reduced pressure and 50 g of crushed ice was added to the residue. The so formed mixture was extracted with ethyl acetate (100 ml, 2×50 ml). The combined organic layers were washed with water (20 ml) brine (50 ml) and dried over MgSO4. The solvent was removed in vacuo and the residue was chromatographed on silica gel. Elution with methanol in chloroform (0% -3%) gave the title compound 9a as an amorphous solid (0.5 g, 37%).

Workup

  1. additionwas added in small portions under an atmosphere of nitrogen
  2. customwas slowly brought to room temperature
  3. customThe solvent was removed under reduced pressure and 50 g of crushed ice
  4. additionwas added to the residue
  5. customThe so formed mixture
  6. extractionwas extracted with ethyl acetate (100 ml, 2×50 ml)
  7. washThe combined organic layers were washed with water (20 ml) brine (50 ml)
  8. dry with materialdried over MgSO4
  9. customThe solvent was removed in vacuo
  10. customthe residue was chromatographed on silica gel
  11. washElution with methanol in chloroform (0% -3%)

Sources & evidence

ORD record
ord-30fc76a34161439eb3996a9c416ff627
Source dataset
uspto-grants-2000_10
Patent number
US06133485

Reaction notes

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