Potassium Phosphate, Tribasic → 7-(2-Trifluoromethyl-phenyl)-quinolin-4-ol

HRID 968559Notes

Reaction equation

HRID 968559 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.O.C1(C)C=CC=CC=1>[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 178516426HCID 178516426, compound

Product 1

HCID 1785163737-(2-Trifluoromethyl-phenyl)-quinolin-4-olYield 6.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 7-chloroquinolin-4-ol (1000 mg, 5.55 mmol,) 2-(trifluoromethyl)phenylboronic acid (1583 mg, 8.33 mmol) and toluene (50 mL), and bubble nitrogen into the solution for 10 minutes. Add palladium acetate (25 mg, 0.11 mmol), 2-(dicyclohexylphosphino)biphenyl (78 mg, 0.22 mmol), and K3PO4 (2353 mg, 11.1 mmol) and heat at 90° C. for 16 hours. Let cool, add water (25 mL) and EtOAc (50 mL), and remove any insoluble material by filtration. Separate the EtOAc layer, and extract the aqueous layer twice with EtOAc (25 mL each). Combine the EtOAc extracts, dry (Na2SO4), and evaporate. Purify by silica gel chromatography (94% CH2Cl2/5% MeOH/1% NH4OH) to provide 110 mg of 7-(2-Trifluoromethyl-phenyl)-quinolin-4-ol as a white solid.

Workup

  1. temperatureLet cool
  2. customremove any insoluble material
  3. filtrationby filtration
  4. customSeparate the EtOAc layer
  5. extractionextract the aqueous layer twice with EtOAc (25 mL each)
  6. dry with materialdry (Na2SO4)
  7. customevaporate
  8. customPurify by silica gel chromatography (94% CH2Cl2/5% MeOH/1% NH4OH)

Sources & evidence

ORD record
ord-5989b11a57554599ada5294578c71bd5
Source dataset
uspto-grants-2007_12
Patent number
US07304059B2

Reaction notes

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