Sodium hydride → (2R,3R)-2-(4-Fluorophenyl)-3-(2H-1,2,3-triazol-2-yl)-1-(1H-1,2, 4-triazol-1-yl)-2-butanol

HRID 1491723Notes

Reaction equation

HRID 1491723 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.[H-].[Na+].[F:8][C:9]1[CH:14]=[CH:13][C:12]([C@@:15]2([CH2:19][N:20]3[CH:24]=[N:23][CH:22]=[N:21]3)[C@H:17]([CH3:18])[O:16]2)=[CH:11][CH:10]=1>CN(C)C=O>[F:8][C:9]1[CH:14]=[CH:13][C:12]([C@:15]([OH:16])([C@H:17]([N:2]2[N:3]=[CH:4][CH:5]=[N:1]2)[CH3:18])[CH2:19][N:20]2[CH:24]=[N:23][CH:22]=[N:21]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10443975(2R,3S)-2-(4-Fluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxiraneHCID 178418936HCID 178418936, compound

Product 1

HCID 10357540(2R,3R)-2-(4-Fluorophenyl)-3-(2H-1,2,3-triazol-2-yl)-1-(1H-1,2, 4-triazol-1-yl)-2-butanolYield 23.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 1H-1,2,3-triazole (1.49 g) in dimethylformamide (35 ml) was added portionwise 60% sodium hydride in oil (0.63 g) under ice-cooling. Ten minutes later, to the mixture was added (2R,3S)-2-(4-fluorophenyl)-3-methyl-2-[(1H-1,2, 4-triazol-1-yl)methyl]oxirane (3.34 g), followed by stirring for 4 hours at 80° C. After cooling, the mixture was concentrated. The residue was partitioned with ethyl acetate (300 ml) and saturated saline. The organic layer was washed with saturated saline, dried and distilled under reduced pressure. The residue was purified by silica gel column chromatography (silica gel 150 g, eluent: dichloro methane/acetone=3:2>1:1). The first eluate gave Compound 36 (1.02 g), followed by recrystallization from dichloromethane-diisopropyl ether to afford colorless prisms. Then a second eluate gave Compound 37 (1.05 g), followed by recrystallization from dichloromethane-diisopropyl ether to afford a colorless crystalline powder.

Workup

  1. temperaturecooling
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated
  4. customThe residue was partitioned with ethyl acetate (300 ml) and saturated saline
  5. washThe organic layer was washed with saturated saline
  6. customdried
  7. distillationdistilled under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (silica gel 150 g, eluent: dichloro methane/acetone=3:2>1:1)

Sources & evidence

ORD record
ord-4f83100ac78c46f69c720f8c762a111e
Source dataset
uspto-grants-1994_12
Patent number
US05371100

Reaction notes

Loading…