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

HRID 379665Notes

Reaction equation

HRID 379665 reaction equation
[H-].[Na+].N1C=[CH:6][N:5]=[N:4]1.[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]1([C@H:19]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH3:20])[CH2:18][O:17]1.[CH3:28][N:29](C=O)C>>[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]([OH:17])([C@H:19]([O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1)[CH3:20])[CH2:18][N:5]1[CH:6]=[N:29][CH:28]=[N:4]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 98606092-(2,5-Difluorophenyl)-2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]oxiraneHCID 178418936HCID 178418936, compound

Product 1

HCID 9928483(3R)-2-(2,5-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol

Procedure

To a suspension of NaH (38.5 g, 60% in mineral oil, 0.962 mol, washed with hexane three times) in DMF (1 L) cooled in an ice-bath was added triazole (133 g, 1.92 mol) portionwise over a period of 30 min. After completion of the addition, the mixture was warmed to room temperature. The above crude 2-(2,5-Difluorophenyl)-2-[(1R)-1-(3,4,5,6,-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane was added and the mixture was heated at 70° C. for 8 h. After cooling to room temperature, the reaction mixture was quenched with water (1 L) and the mixture was extracted with EtOAc (1 L×3). The EtOAc layer was combined and washed with water and brine, dried over MgSO4, and evaporated under reduced pressure. The portion of residue was chromatographed on silicagel for analysis (n-hexane: EtOAc=4:1˜1:5) to give pure (3R)-2-(2,5-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol.

Workup

  1. temperaturecooled in an ice-bath
  2. additionAfter completion of the addition
  3. temperaturethe mixture was heated at 70° C. for 8 h
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was quenched with water (1 L)
  6. extractionthe mixture was extracted with EtOAc (1 L×3)
  7. washwashed with water and brine
  8. dry with materialdried over MgSO4
  9. customevaporated under reduced pressure
  10. customThe portion of residue was chromatographed on silicagel for analysis (n-hexane: EtOAc=4:1˜1:5)

Sources & evidence

ORD record
ord-8d39f9f853594c228eb3bd37ddf5aa75
Source dataset
uspto-grants-2001_10
Patent number
US06300353B1

Reaction notes

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