8-Hydroxyquinoline → 3-(2-((Dimethylamino)methyl)-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline
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.[NH:13]1[CH:17]=[CH:16][N:15]=[C:14]1[CH2:18][N:19]([CH3:21])[CH3:20].OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[CH3:20][N:19]([CH2:18][C:14]1[N:13]([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:17]=[CH:16][N:15]=1)[CH3:21]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 120 °C
Procedure
3-Amino-5-bromobenzotrifluoride (6 g, 25 mmol) and 1-(1H-imidazol-2-yl)-N,N-dimethylmethanamine (3.7 g, 29.6 mmol) were dissolved in anhydrous DMSO (25 mL). To this was added CuI (0.95 g, 7.5 mmol), 8-hydroxy quinoline (0.72 g, 7.5 mmol) and K2CO3 (6.9 g, 50 mmol). The mixture was stirred vigorously and degassed with N2 for 15 minutes. The flask was then equipped with a condenser and heated at 120° C. for 18 h. The resultant heterogeneous mixture was cooled to rt, poured into 14% aq. NH4OH (100 mL) and extracted with EtOAc (3×300 ml). The combined extracts were dried over NaSO4 and concentrated in vacuo. The residue was chromatographed over silica gel eluting with MeOH/DCM (5:95) to furnish 3.5 g of the desired product as a tan colored material: 285 m/z (M+H).
Workup
- customdegassed with N2 for 15 minutes
- customThe flask was then equipped with a condenser
- temperatureThe resultant heterogeneous mixture was cooled to rt
- additionpoured into 14% aq. NH4OH (100 mL)
- extractionextracted with EtOAc (3×300 ml)
- dry with materialThe combined extracts were dried over NaSO4
- concentrationconcentrated in vacuo
- customThe residue was chromatographed over silica gel eluting with MeOH/DCM (5:95)
Sources & evidence
- ORD record
- ord-e2904fb811734152a121a2d73383760d
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09278971B2
Reaction notes
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