Benzeneacetonitrile, 4-methoxy- → 3-(2-Fluoro-4-trifluoromethyl-phenyl)-5-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamine

HRID 1639692Notes

Reaction equation

HRID 1639692 reaction equation
C[O-].[Na+].[CH3:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]#[N:14])=[CH:8][CH:7]=1.[N:15]([C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=1[F:28])=[N+:16]=[N-:17]>CO>[F:28][C:19]1[CH:20]=[C:21]([C:24]([F:26])([F:27])[F:25])[CH:22]=[CH:23][C:18]=1[N:15]1[C:13]([NH2:14])=[C:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH3:4])=[CH:7][CH:8]=2)[N:17]=[N:16]1

Participants

5

Reactant 3

HCID 66031Benzeneacetonitrile, 4-methoxy-HCID 10942334Sodium MethoxideHCID 866450681-Azido-2-fluoro-4-(trifluoromethyl)benzene

Product 1

HCID 252156773-(2-Fluoro-4-trifluoromethyl-phenyl)-5-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamineYield 1.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred and ice-cooled solution of sodium methoxide (1.659 g, 30.7146 mmol) in methanol (50 ml), 4-methoxyphenylacetonitrile (3.728 g, 24.5717 mmol) and 1-azido-2-fluoro-4-trifluoromethyl-benzene (4.200 g, 20.4764 mmol) are added portion wise and the mixture is allowed attain room temperature spontaneously and refluxed overnight. The resulting reaction mixture is concentrated, added water, and extracted with chloroform (3×100 mL). The combined organic layers are dried over MgSO4, filtered and concentrated to afford a brownish gummy material (5.900 g, 82% mass balance). The crude residue is purified by column chromatography over silica gel (230-400 mesh), eluting with 15% ethylacetate in hexane, to obtain the title compound as a grey solid (0.120 g, 1.5% yield). A major impurity isolated and characterized is 5-(4-methoxy-phenyl)-3-(2-methoxy-4-trifluoromethyl-phenyl)-3H-[1,2,3]triazol-4-ylamine (2.400 g, ˜33% yield).

Workup

  1. additionare added portion wise
  2. customis allowed attain room temperature
  3. temperaturerefluxed overnight
  4. customThe resulting reaction mixture
  5. concentrationis concentrated
  6. additionadded water
  7. extractionextracted with chloroform (3×100 mL)
  8. dry with materialThe combined organic layers are dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a brownish gummy material (5.900 g, 82% mass balance)
  12. customThe crude residue is purified by column chromatography over silica gel (230-400 mesh)
  13. washeluting with 15% ethylacetate in hexane

Sources & evidence

ORD record
ord-848cecca055f4c178b53ca0a3eb22bdb
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

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