Ammonia → 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline

HRID 706836Notes

Reaction equation

HRID 706836 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1)[NH2:5].[CH3:13][C:14]1[N:15]=[CH:16][NH:17][CH:18]=1.C([O-])([O-])=O.[K+].[K+].OC1C=CC=C2C=1N=CC=C2.N>CS(C)=O.[Cu]I.CCOC(C)=O.O>[CH3:13][C:14]1[N:15]=[CH:16][N:17]([C:2]2[CH:3]=[C:4]([CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=2)[NH2:5])[CH:18]=1

Participants

10

Reactant 5

HCID 222AmmoniaHCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 27358803-Bromo-5-(trifluoromethyl)anilineHCID 178418800HCID 178418800, compound

Product 1

HCID 120028253-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)anilineYield 59.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 3-bromo-5-(trifluoromethyl)aniline (4.8 g, 20 mmol), 4-methylimidazole (1.97 g, 24 mmol), K2CO3 (3.04 g, 22 mmol), CuI (0.57 g, 3 mmol) and 8-hydroxyquinoline (0.44 g, 3 mmol) in 20 mL DMSO was stirred at 120° C. in a sealed tube under Ar2 for 16 hrs. The mixture was cooled down to 50° C. and 28% aq ammonia (10 mL) was added. The mixture was maintained at this temperature for 1 h. After cooling to rt, H2O and EtOAc were added. The aqueous layer was extracted with EtOAc (60 mL×3) and the organic layer was washed with brine, dried with Na2SO4, after filtration, the filtrate was concentrated under reduced pressure and purified by chromatography on silica gel (CH2Cl2/CH3OH 97:3) to give 2.85 g product as pale yellow solid (59.1%). 1H NMR (300 MHz, CDCl3) δ: 7.76 (1 H, s), 7.01 (1 H, s), 6.94 (1 H, s), 6.84 (1 H, s), 6.78 (1 H, s), 4.11 (2 H, brs), 2.29 (3 H, s). LCMS: m/z [M+H]+ 242.0966.

Workup

  1. temperatureThe mixture was cooled down to 50° C.
  2. temperatureThe mixture was maintained at this temperature for 1 h
  3. temperatureAfter cooling to rt
  4. extractionThe aqueous layer was extracted with EtOAc (60 mL×3)
  5. washthe organic layer was washed with brine
  6. dry with materialdried with Na2SO4
  7. filtrationafter filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. custompurified by chromatography on silica gel (CH2Cl2/CH3OH 97:3)

Sources & evidence

ORD record
ord-e8b7caab13e04324a2f56b5a41cec94c
Source dataset
uspto-grants-2015_11
Patent number
US09174996B2

Reaction notes

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