Potassium Carbonate → 2-Furan-3-yl-6-methoxy-1H-indole

HRID 2409958Notes

Reaction equation

HRID 2409958 reaction equation
FC(F)(F)C([NH:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=1I)=O.[O:17]1[CH:21]=[CH:20][C:19]([C:22]#[C:23][Si](C)(C)C)=[CH:18]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[Cl-].[Na+].O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.C(#N)C.C(N(CC)CC)C>[O:17]1[CH:21]=[CH:20][C:19]([C:22]2[NH:5][C:6]3[C:7]([CH:23]=2)=[CH:8][CH:9]=[C:10]([O:12][CH3:13])[CH:11]=3)=[CH:18]1

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 16217672[2-(Furan-3-yl)ethynyl]trimethylsilaneHCID 221434932,2,2-Trifluoro-N-(2-iodo-5-methoxy-phenyl)-acetamide

Product 1

HCID 867032792-Furan-3-yl-6-methoxy-1H-indoleYield 68.3%

Reagents, catalysts & solvents 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 2,2,2-trifluoro-N-(2-iodo-5-methoxyphenyl)acetamide (1.00 g), furan-3-ylethynyltrimethylsilane (714 mg), bis(triphenylphosphine) palladium(II) dichloride (61 mg), copper(I) iodide (33 mg), triethylamine (0.81 mL), and acetonitrile (15 mL) was added tetrabutylammonium fluoride in tetrahydrofuran solution (1 mol/L, 4.4 mL) at 50° C. This mixture was stirred at 50° C. for 1 hour. Then, potassium carbonate (801 mg) was added thereto, followed by stirring at 50° C. overnight. To the reaction mixture was added saturated brine, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (422 mg). 1H-NMR (CDCl3) δ ppm: 3.86 (3H, s), 6.51-6.56 (1H, m), 6.64-6.69 (1H, m), 6.78 (1H, dd, J=2.3, 8.5 Hz), 6.84-6.90 (1H, m), 7.42-7.51 (2H, m), 7.67-7.73 (1H, m), 7.78-8.13 (1H, br).

Workup

  1. stirringby stirring at 50° C. overnight
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-7f70ba1d5b3742818b70528496818d22
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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