Water → HCID 462669, compound

HRID 2397010Notes

Reaction equation

HRID 2397010 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]1([C@H:19]([N:21]2[CH:25]=[CH:24][N:23]=[N:22]2)[CH3:20])[CH2:18][O:17]1.O>CN(C)C=O.C(OCC)(=O)C>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]([OH:17])([C@H:19]([N:21]1[CH:25]=[CH:24][N:23]=[N:22]1)[CH3:20])[CH2:18][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 15337566HCID 15337566, compound

Product 1

HCID 462669HCID 462669, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1H-1,2,4-Triazole (63 mg) was added under ice-cooling to a dispersion of 60% sodium hydride in oil (36 mg) in dimethylformamide (1.5 ml) and the resulting mixture was stirred for 10 minutes at room temperature. To the mixture was added a solution of (2S)-2-(2,4-difluorophenyl)-2-[(1R)-1-(1H-1,2,3-triazol-1-yl)ethyl]oxirane (116 mg) in dimethylformamide (0.8 ml), followed by heating for 5 hours at 50° C. and cooling. Cold water (10 ml) and ethyl acetate (20 ml) were added to the reaction mixture. The separated aqueous layer was extracted twice with ethyl acetate. The combined ethyl acetate layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate and distilled under reduced pressure. The residue was purified by silica gel column chromatography (acetone/dichlormethane=1:2→1:1). The obtained crystals were recrystallized from diisopropyl ether to give the title compound (Compound 6, 66 mg, 45%) as colorless crystals.

Workup

  1. temperatureby heating for 5 hours at 50° C.
  2. temperaturecooling
  3. extractionThe separated aqueous layer was extracted twice with ethyl acetate
  4. washThe combined ethyl acetate layers were washed with water and saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (acetone/dichlormethane=1:2→1:1)
  8. customThe obtained crystals were recrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-0fa15bb071cf4ce99508d503395239dc
Source dataset
uspto-grants-1996_02
Patent number
US05495024

Reaction notes

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