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

HRID 1654199Notes

Reaction equation

HRID 1654199 reaction equation
[H-].[Na+].N1C=[CH:6][N:5]=[N:4]1.[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][C@@H:15]([C:17]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[CH2:19][O:18]1)[CH3:16].O.[CH3:29][N:30](C)C=O>>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C:17]([OH:18])([C@H:15]([O:14][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][O:8]1)[CH3:16])[CH2:19][N:5]1[CH:6]=[N:30][CH:29]=[N:4]1

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 542112042H-Pyran, 2-[(1R)-1-[2-(2,4-difluorophenyl)oxiranyl]ethoxy]tetrahydro-HCID 178418936HCID 178418936, compound

Product 1

HCID 14978397(3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol

Procedure

In dimethylformamide (50 ml) was dispersed 60% sodium hydride (2.64 g) in mineral oil, to which was added, under ice-cooling, triazole (6.84 g), and the mixture was stirred for 15 minutes. To the mixture was added a dimethylformamide solution (10 ml) of 2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxirane (4.7 g). The resultant mixture was heated for 3 hours at 80° C. The reaction mixture was cooled, which was then poured into cold water (200 ml), followed by extraction with ethyl acetate (150 ml) three times. Ethyl acetate layers were combined, washed with water (100 ml×3) and a saturated aqueous solution (100 ml) of sodium chloride successively, and dried over anhydrous sodium sulfate, followed by distilling off the solvent. The residue was purified by means of a silica gel chromatography (eluent: dichloromethane-ethyl acetate-acetone=6:1:1) to afford (3R)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H- 1,2,4-triazol-1-yl)-2-butanol (4.4 g) as a colorless viscous oil.

Workup

  1. additionto which was added, under ice-
  2. temperaturecooling
  3. temperatureThe reaction mixture was cooled
  4. extractionfollowed by extraction with ethyl acetate (150 ml) three times
  5. washwashed with water (100 ml×3)
  6. dry with materiala saturated aqueous solution (100 ml) of sodium chloride successively, and dried over anhydrous sodium sulfate
  7. distillationby distilling off the solvent
  8. customThe residue was purified by means of a silica gel chromatography (eluent: dichloromethane-ethyl acetate-acetone=6:1:1)

Sources & evidence

ORD record
ord-89eea257e5f44cd59351b3de205f5d4f
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

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