4-(Trifluoromethyl)aniline → 6-[Bis(4-chlorophenyl)methyl]-4-[[4-(trifluoromethyl)phenyl]amino]quinolin-2-ol

HRID 1778219Notes

Reaction equation

HRID 1778219 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3Br)=[CH:4][CH:3]=1.[F:28][C:29]([F:38])([F:37])[C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3[NH:34][C:33]2[CH:35]=[CH:36][C:30]([C:29]([F:28])([F:37])[F:38])=[CH:31][CH:32]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 99644-(Trifluoromethyl)anilineHCID 10796Cesium carbonateHCID 178515443HCID 178515443, compound

Product 1

HCID 1785164076-[Bis(4-chlorophenyl)methyl]-4-[[4-(trifluoromethyl)phenyl]amino]quinolin-2-ol

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 8-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 6-[bis(4-chlorophenyl)methyl]-4-bromoquinolin-2-ol (150 mg, 0.33 mmol, 1.00 equip), 4-(trifluoromethyl)aniline (78.9 mg, 0.49 mmol, 1.50 equip), Pd2(dba)3 (30 mg, 0.03 mmol, 0.10 equip), dppf (63.4 mg, 0.11 mmol, 0.35 equip), Cs2CO3 (266 mg, 0.82 mmol, 2.50 equip), and 1,4-dioxane (3 mL). The resulting solution was stirred overnight at 100° C. The reaction was then quenched by the addition of water (100 mL). The resulting solution was extracted with ethyl acetate (3×50 mL) and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (20:1). The resulting residue was recrystallized from ethyl acetate:petroleum ether in the ratio of 1:10 to yield 6-[bis(4-chlorophenyl)methyl]-4-[[4-(trifluoromethyl)phenyl]amino]quinolin-2-ol as a light yellow solid.

Workup

  1. customInto a 8-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe reaction was then quenched by the addition of water (100 mL)
  4. extractionThe resulting solution was extracted with ethyl acetate (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solids were filtered out
  7. concentrationThe resulting mixture was concentrated under vacuum
  8. customThe resulting residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-87b323ee37d64a2e962746b41416f4e4
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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