Imidazole → 3-(1H-Imidazol-1-YL)-5-(trifluoromethyl)aniline

HRID 1622502Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:5]=[C:6](Br)[CH:7]=1.OC1C=CC=C2C=1N=CC=C2.[NH:24]1[CH:28]=[CH:27][N:26]=[CH:25]1.C(=O)([O-])[O-].[K+].[K+].[OH-].[NH4+]>CS(C)=O.[Cu]I.CCOC(C)=O.O>[N:24]1([C:6]2[CH:7]=[C:2]([CH:3]=[C:4]([C:9]([F:10])([F:12])[F:11])[CH:5]=2)[NH2:1])[CH:28]=[CH:27][N:26]=[CH:25]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-Amino-5-bromobenzotrifluoride (4.0 g, 0.0167 mol), 8-hydroxy quinoline (0.362 g, 0.0025 mol), CuI (0.476 g, 0.025 mol), imidazole (1.36 g, 0.0199 mol), and potassium carbonate (2.52 g, 0.0183 mol) in 17 mL of DMSO (degassed with argon for ˜10 min) was heated at 120° C. under an atmosphere of argon for 15 h; the HPLC indicated no starting material. A 14% aqueous solution of ammonium hydroxide was added to the cooled mixture and this was stirred for 1 h at ambient temperature. Water (50 mL) and EtOAc (200 mL) were added and the aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by silica gel flash chromatography (eluted with EtOAc/hexanes) to provide 2.51 g of product.

Workup

extractionthe aqueous layer was extracted with EtOAc (3×30 mL)
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated
customThe crude product was purified by silica gel flash chromatography (eluted with EtOAc/hexanes)

Sources & evidence

ORD record: ord-2d4b599547994c949881f5f72dc53400
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778942B2

Reaction notes

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