1H-1,2,4-Triazole → (3R)-2-(4-chlorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol

HRID 1491713Notes

Reaction equation

HRID 1491713 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([C@H:18]([O:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][O:22]3)[CH3:19])[CH2:17][O:16]2)=[CH:11][CH:10]=1>CN(C)C=O>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([OH:16])([C@H:18]([O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH3:19])[CH2:17][N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 537335332-(4-chlorophenyl)-2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane

Product 1

HCID 54228022(3R)-2-(4-chlorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanolYield 81.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1H-1,2,4-Triazole (42.1 g) was added portionwise to a dispersion of 60% sodium hydride in oil (22.2 g) in dimethylformamide (300 ml) under ice-cooling, followed by stirring for 15 minutes. To the mixture was added a solution of the crude product of 2-(4-chlorophenyl)-2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane (52 g) in dimethylformamide (50 ml), followed by stirring for 4 hours at 80° C. After cooling, the reaction mixture was poured into ice water (400 ml) and extracted three times with ethyl acetate (200 ml). The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate and distilled under reduced pressure. The residue was subjected to silica gel column chromatography (eluent: hexane/ethyl acetate=3:2→ethyl acetate/acetone=4:1) to give (3R)-2-(4-chlorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (53 g) as a colorless amorphous substance.

Workup

  1. temperaturecooling
  2. stirringby stirring for 4 hours at 80° C
  3. temperatureAfter cooling
  4. extractionextracted three times with ethyl acetate (200 ml)
  5. washThe organic layer was washed with water and saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationdistilled under reduced pressure

Sources & evidence

ORD record
ord-3dc857a75a5b4a6c8c9aea4388494725
Source dataset
uspto-grants-1994_12
Patent number
US05371100

Reaction notes

Loading…