Water → HCID 11723569, compound

HRID 2397009Notes

Reaction equation

HRID 2397009 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[N:25]=[N:24][CH: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[N:25]=[N:24][CH: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 10753283HCID 10753283, compound

Product 1

HCID 11723569HCID 11723569, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1H-1,2,4-Triazole (48 mg) was added to a dispersion of 60% sodium hydride in oil (27 mg) in dimethylformamide (1.1 ml) under ice-cooling and the resulting mixture was stirred for 10 minutes at room temperature. After addition of a solution of (2S)-2-(2,4-difluorophenyl)-2-[(1R)-1-(2H-tetrazol-2-yl)ethyl]oxirane (89 mg) in dimethylformamide (0.7 ml), the mixture was heated for 5 hours at 50° C. and cooled. 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 organic 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 (eluent: ethyl acetate/hexane=1:1→2:1→ethyl acetate) to give the title compound (Compound 4, 60 mg, 53%) as a colorless oily substance.

Workup

  1. temperaturecooling
  2. temperaturethe mixture was heated for 5 hours at 50° C.
  3. temperaturecooled
  4. extractionThe separated aqueous layer was extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with water and saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationdistilled under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1:1→2:1→ethyl acetate)

Sources & evidence

ORD record
ord-e3778d94df694c4696553dca6bb4ed80
Source dataset
uspto-grants-1996_02
Patent number
US05495024

Reaction notes

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