Sodium hydride → (5RS)-3-(3-Fluoro-4-(1,2,3-triazol-1-yl)phenyl)-5-(1,2,3-triazol-1-ylmethyl)-4,5-dihydroisoxazole

HRID 1793851Notes

Reaction equation

HRID 1793851 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[N:4]1.[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[N:23]3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1F>CN(C)C=O>[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[N:23]3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1[N:3]1[CH:7]=[CH:6][N:5]=[N:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11334553HCID 11334553, compoundHCID 178418936HCID 178418936, compound

Product 1

HCID 9879819(5RS)-3-(3-Fluoro-4-(1,2,3-triazol-1-yl)phenyl)-5-(1,2,3-triazol-1-ylmethyl)-4,5-dihydroisoxazoleYield 3.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A slurry of sodium hydride (60% in oil, 44 mg, 1.1 mM) in anhydrous N,N-dimethylformamide (1 ml) was stirred under an atmosphere of nitrogen and treated dropwise with a solution of 1,2,3-triazole (76 mg, 1.1 mM) in anhydrous N,N-dimethylformamide (1 ml) at 0°. The mixture was allowed to warm to ambient temperature over 20 minutes, then a solution of (5RS)-3-(3,4-difluorophenyl)-5-(1,2,3-triazol-1-yl-methyl)-4,5-dihydroisoxazole (264 mg, 1 mM) in anhydrous N,N-dimethylformamide (2 ml) added, and the mixture stirred at 70° for 16 hours. After cooling, the mixture was partitioned between aqueous sodium bicarbonate solution (40 ml) and ethyl acetate (40 ml), and the organic extract washed with water (40 ml) and brine (40 ml). After drying (magnesium sulfate) and evaporation, the crude product was chromatographed on a 20 g silica Mega Bond Elut® column, eluting with ethyl acetate. Relevant fractions were combined to give the desired product (12 mg).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between aqueous sodium bicarbonate solution (40 ml) and ethyl acetate (40 ml)
  3. extractionthe organic extract
  4. washwashed with water (40 ml) and brine (40 ml)
  5. customAfter drying
  6. custom(magnesium sulfate) and evaporation
  7. customthe crude product was chromatographed on a 20 g silica Mega Bond Elut® column
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-1e8c06cb7a30414e9ca0ba08fcea7f14
Source dataset
uspto-grants-2006_04
Patent number
US07022705B2

Reaction notes

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