Potassium Phosphate, Tribasic → Methyl 6-(6,7-dimethoxyquinolin-4-yloxy)benzofuran-3-carboxylate

HRID 1865215Notes

Reaction equation

HRID 1865215 reaction equation
[OH:1][C:2]1[CH:14]=[CH:13][C:5]2[C:6]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][O:8][C:4]=2[CH:3]=1.Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH3:29])=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:27][O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][C:22]=1[O:28][CH3:29])[N:19]=[CH:18][CH:17]=[C:16]2[O:1][C:2]1[CH:14]=[CH:13][C:5]2[C:6]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, Tribasic2×HCID 4596104-Chloro-6,7-dimethoxyquinoline3×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl3×HCID 59577559Methyl 6-hydroxybenzofuran-3-carboxylate

Product 1

HCID 69019235Methyl 6-(6,7-dimethoxyquinolin-4-yloxy)benzofuran-3-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 6-hydroxybenzofuran-3-carboxylate (312 mg, 1.62 mmol) was dissolved in N,N-dimethylformamide (5 mL) then added 4-chloro-6,7-dimethoxyquinoline (451 mg, 2.02 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl (77 mg, 0.162 mmol), palladium acetate (36 mg, 0.162 mmol) and potassium phosphate (687 mg, 3.24 mmol). The reaction mixture was stirred at 100° C. overnight. Additional palladium acetate (36 mg, 0.162 mmol) was added to the mixture and the heating was continued at 100° C. for 4 h. Additional 4-chloro-6,7-dimethoxyquinoline (181 mg, 0.812 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl (77 mg, 0.162 mmol) were added to the mixture and heating at 100° C. was continued for 2 days. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The remaining orange oil was redissolved in toluene (5 mL) and DMF (1 mL) then added 4-chloro-6,7-dimethoxyquinoline (225 mg, 1.01 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl (38 mg, 0.080 mmol), palladium acetate (18 mg, 0.080 mmol) and potassium phosphate (343 mg, 1.62 mmol). The reaction mixture was heated at 100° C. overnight and concentrated in vacuo. The remaining orange-black oil was purified by silica gel chromatography (1% to 2% methanol in dichloromethane) to afford methyl 6-(6,7-dimethoxyquinolin-4-yloxy)benzofuran-3-carboxylate as a light yellow solid. MS (ESI, pos. ion) m/z: 380.1 (M+1).

Workup

  1. waitthe heating was continued at 100° C. for 4 h
  2. temperatureheating at 100° C.
  3. waitwas continued for 2 days
  4. filtrationThe reaction mixture was filtered
  5. concentrationthe filtrate was concentrated in vacuo
  6. dissolutionThe remaining orange oil was redissolved in toluene (5 mL)
  7. temperatureThe reaction mixture was heated at 100° C. overnight
  8. concentrationconcentrated in vacuo
  9. customThe remaining orange-black oil was purified by silica gel chromatography (1% to 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e6311db453e7497696d477d60e619465
Source dataset
uspto-grants-2009_12
Patent number
US07626030B2

Reaction notes

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