Water → (3S)-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 1654191Notes

Reaction equation

HRID 1654191 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>C(OCC)(=O)C>[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

7

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 571648292-[(1S)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxiraneHCID 178418936HCID 178418936, compound

Product 1

HCID 14978398(3S)-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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

In dimethylformamide (5 ml) was dispersed 60% sodium hydride in oil (0.23 g), to which was added triazole (0.59 g) under ice-cooling, followed by stirring for 15 minutes. To the resultant mixture was added a dimethylformamide solution (1 ml) of 2-[(1S)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxirane (0.40 g), which was heated for three hours at 80° C. The reaction mixture was cooled, after which were added cold water (1.0 ml) and ethyl aceate (50 ml), and the mixture was shaken. The aqueous layer was subjected to extraction with ethyl acetate twice. Ethyl acetate layers were combined, washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate, followed by distilling off the solvent under reduced pressure. The residue was purified by means of a silica gel chromatography (eluent, dichloromethane:ethyl acetate:acetone=6:1:1). The resultant waxy product was further subjected to reprecipitation twice from ethyl acetate-hexane to afford (3S)-2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (0.22 g) as a colorless waxy product.

Workup

  1. temperaturecooling
  2. temperatureThe reaction mixture was cooled
  3. stirringthe mixture was shaken
  4. extractionThe aqueous layer was subjected to extraction with ethyl acetate twice
  5. washwashed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationby distilling off the solvent under reduced pressure
  8. customThe residue was purified by means of a silica gel chromatography (eluent, dichloromethane:ethyl acetate:acetone=6:1:1)
  9. customThe resultant waxy product was further subjected to reprecipitation twice from ethyl acetate-hexane

Sources & evidence

ORD record
ord-d21d5053b2ec45629c2ea4b6548f3d26
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

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