1H-1,2,4-Triazole → 2-Methoxy-4-(1H-1,2,4-triazol-1-yl)aniline

HRID 1630337Notes

Reaction equation

HRID 1630337 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([O:9][CH3:10])[CH:3]=1.[NH:11]1[CH:15]=[N:14][CH:13]=[N:12]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C.[Cu]I>[CH3:10][O:9][C:4]1[CH:3]=[C:2]([N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:8]=[CH:7][C:5]=1[NH2:6]

Participants

7

Reactant 3

HCID 92571H-1,2,4-Triazole2×HCID 10796Cesium carbonate2×HCID 4592574-Bromo-2-methoxyaniline

Product 1

HCID 450914512-Methoxy-4-(1H-1,2,4-triazol-1-yl)anilineYield 47%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-bromo-2-methoxyaniline (208 mg, 1.03 mmol), 1,2,4-triazole (80 mg, 1.13 mmol), Cs2CO3 (0.67 g, 2.06 mmol) and CuI (20 mg, 0.103 mmol) in DMF was heated at 110° C. for 20 h. Further portions of 1,2,4-triazole (0.1 g, 1.44 mmol), Cs2CO3 (0.67 g, 2.06 mmol) and CuI (0.1 g, 0.52 mmol) were added and the mixture was heated a further 72 h at 110° C. The mixture was cooled, diluted with ethyl acetate (20 mL) and washed with water (2×20 mL). The combined aqueous washes were re-extracted with ethyl acetate (20 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) gave 2-methoxy-4-(1H-1,2,4-triazol-1-yl)aniline as a light red solid (92 mg, 47%). 1H NMR (400 MHz, CDCl3): δ 8.41 (s, 1H); 8.05 (s, 1H); 7.11 (d, J=2.3, 1H); 6.99 (dd, J=8.3, 2.3, 1H); 6.74 (d, J=8.3, 1H); 3.97 (s, 2H); 3.92 (s, 3H).

Workup

  1. temperaturethe mixture was heated a further 72 h at 110° C
  2. temperatureThe mixture was cooled
  3. washwashed with water (2×20 mL)
  4. extractionThe combined aqueous washes were re-extracted with ethyl acetate (20 mL)
  5. customThe combined organics were passed through a phase separation cartridge
  6. customthe solvent removed under reduced pressure
  7. customPurification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-bfe89ddad8c5466c80c3a49e52cda94b
Source dataset
uspto-grants-2014_07
Patent number
US08791130B2

Reaction notes

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