5-Bromo-2-(3,5-dimethylphenyl)quinoline → 2-(3,5-Dimethylphenyl)-5-(3,3,3-trifluoropropyl)quinoline

HRID 1056443Notes

Reaction equation

HRID 1056443 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[CH:13]=1)=[N:7]2.[I-].[F:21][C:22]([F:27])([F:26])[CH2:23][CH2:24][Zn+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C1C=CC=C(N(C)C)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1)C>[CH3:19][C:14]1[CH:13]=[C:12]([C:6]2[CH:5]=[CH:4][C:3]3[C:8](=[CH:9][CH:10]=[CH:11][C:2]=3[CH2:24][CH2:23][C:22]([F:27])([F:26])[F:21])[N:7]=2)[CH:17]=[C:16]([CH3:18])[CH:15]=1

Participants

6

Reactant 2

HCID 682876225-Bromo-2-(3,5-dimethylphenyl)quinolineHCID 178506322HCID 178506322, compound

Product 1

HCID 1212668312-(3,5-Dimethylphenyl)-5-(3,3,3-trifluoropropyl)quinolineYield 81%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 441561692'-(Dicyclohexylphosphino)-N2,N2,N6,N6-tetramethyl[1,1'-biphenyl]-2,6-diamineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

5-bromo-2-(3,5-dimethylphenyl)quinoline (1.15 g, 3.68 mmol), Palladium(II) acetate (0.017 g, 0.074 mmol), and CPhos (0.064 g, 0.147 mmol) were charged into a flask and diluted with 100 mL of tetrahydrofuran. This mixture was degassed with nitrogen followed by the addition of (3,3,3-trifluoropropyl)zinc(II) iodide (1.07 g, 3.68 mmol) via syringe. The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with aqueous ammonium chloride then was extracted 2×200 mL of ethyl acetate, and dried over sodium sulfate. The crude material was coated on Celite and purified by column chromatography using a 20% DCM in Heptanes solvent system. The product was recrystallized in heptanes to afford 0.90 g of the target compound (81% yield).

Workup

  1. customThis mixture was degassed with nitrogen
  2. customThe reaction mixture was quenched with aqueous ammonium chloride
  3. extractionthen was extracted 2×200 mL of ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. custompurified by column chromatography
  6. customThe product was recrystallized in heptanes

Sources & evidence

ORD record
ord-3bf105f449244cd184502ed321901809
Source dataset
uspto-grants-2016_07
Patent number
US09397302B2

Reaction notes

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