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

HRID 655796Notes

Reaction equation

HRID 655796 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>CS(C)=O.[Cu]I>[CH3:13][C:14]1[N:15]=[CH:16][N:17]([C:2]2[CH:3]=[C:4]([NH2:5])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=2)[CH:18]=1

Participants

7

Reactant 4

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

Product 1

HCID 120028253-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 3-bromo-5-(trifluoromethyl)aniline (4.80 g, 20 mmol), 4-methylimidazole (1.97 g, 24 mmol), potassium carbonate (3.04 g, 22 mmol), CuI (0.57 g, 3 mmol), and 8-hydroxyquinoline (0.44 g, 3 mmol) in dry DMSO (20 mL) in a pressure tube was degassed by bubbling N2 into the suspension for 10 minutes while stirring. The tube was sealed tightly. The mixture was heated at 120° C. (oil bath temperature) for 15 h. The mixture was cooled down to 45-50° C. and 14% aq. NH4OH (20 mL) was added. The mixture was maintained at this temperature for 1 h. After cooling to rt, water and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate and the combined organic layers were passed through a short silica gel column to remove most of green/blue Cu salt. The filtrate was dried over sodium sulfate and concentrated on a rotavap. The crude product was recrystallized from EtOAc/hexanes, giving pure pale yellow needles. The mother liquor was concentrated and the residue was purified on silica gel column (5% methanol/methylene chloride), yielding a second crop as pale yellow needles.

Workup

  1. customwas degassed
  2. customby bubbling N2 into the suspension for 10 minutes
  3. customThe tube was sealed tightly
  4. temperatureThe mixture was cooled down to 45-50° C.
  5. addition14% aq. NH4OH (20 mL) was added
  6. temperatureThe mixture was maintained at this temperature for 1 h
  7. temperatureAfter cooling to rt
  8. additionwater and ethyl acetate were added
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. customto remove most of green/blue Cu salt
  11. dry with materialThe filtrate was dried over sodium sulfate
  12. concentrationconcentrated on a rotavap
  13. customThe crude product was recrystallized from EtOAc/hexanes
  14. customgiving pure pale yellow needles
  15. concentrationThe mother liquor was concentrated
  16. customthe residue was purified on silica gel column (5% methanol/methylene chloride)
  17. customyielding a second crop as pale yellow needles

Sources & evidence

ORD record
ord-ade72ef2cf6e478092f055f49b2ff48c
Source dataset
uspto-grants-2011_12
Patent number
US08071609B2

Reaction notes

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