1H-1,2,4-Triazole → 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 1654184Notes

Reaction equation

HRID 1654184 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][CH: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]>CN(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])([CH:15]([O:14][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][O:8]1)[CH3:16])[CH2:19][N:3]1[CH:7]=[N:6][CH:5]=[N:4]1

Participants

5

Reactant 3

HCID 92571H-1,2,4-Triazole2×HCID 24758Sodium hydrideHCID 147064262H-Pyran, 2-[(1R)-1-[2-(2,4-difluorophenyl)oxiranyl]ethoxy]tetrahydro-

Product 1

HCID 200796062-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxy-1-(1H-1,2,4-triazol-1-yl)-2-butanolYield 49.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To N,N-dimethylformamide (700 ml) was added, at room temperature while stirring, 60% sodium hydride in oil (35.2 g) by portions during 10 minutes. The mixture was stirred for 5 minutes at room temperature, to which was added 1H-1,2,4-triazole (25 g) by portions at room temperature during 20 minutes. The reaction mixture was cooled with ice, to which was added 1H-1,2,4-triazole (44.6 g) during 30 minutes with stirring, followed by stirring at room temperature for further 10 minutes. To the resultant mixture was added dropwise 2-[1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxirane (83.4 g) during 5 minutes, which was stirred for 4 hours at 90° C. The reaction mixture was cooled and poured into ice-water (1.5 l), which was subjected to extraction with ethyl acetate (500 ml) for 4 times. The ethyl acetate layer was washed with water (300 ml) 3 times and dried over anhydrous magnesium sulfate. Then the solvent was distilled off to leave a pale yellow oily product. This product was purified by means of a silica gel column chromatography (hexane:acetone=4:1~1:1). The resultant oily product was crystallized from hexane to give 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 (51.4 g) as colorless powder, m.p. 93°-95° C. Elemental Analysis for C17H21F2N3O3 : Calcd.: C, 57.78; H, 5.99; N, 11.89 Found: C, 57.82; H, 6.04; N, 11.77.

Workup

  1. stirringThe mixture was stirred for 5 minutes at room temperature, to which
  2. temperatureThe reaction mixture was cooled with ice, to which
  3. stirringwith stirring
  4. stirringby stirring at room temperature for further 10 minutes
  5. stirringwhich was stirred for 4 hours at 90° C
  6. temperatureThe reaction mixture was cooled
  7. extractionwas subjected to extraction with ethyl acetate (500 ml) for 4 times
  8. washThe ethyl acetate layer was washed with water (300 ml) 3 times
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationThen the solvent was distilled off
  11. customto leave a pale yellow oily product
  12. customThis product was purified by means of a silica gel column chromatography (hexane:acetone=4:1~1:1)
  13. customThe resultant oily product was crystallized from hexane

Sources & evidence

ORD record
ord-16e25a6bf72e45398443e705c2111dee
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

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