Potassium Carbonate → HCID 86698754, compound

HRID 1054761Notes

Reaction equation

HRID 1054761 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=O)([O-])[O-:20].[K+].[K+].Br[C:26]1[CH:35]=[CH:34][C:29]([O:30][CH2:31][CH2:32][OH:33])=[C:28]([F:36])[CH:27]=1>CN(C=O)C.O1CCOCC1.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.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:20])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:35]=[CH:34][C:29]([O:30][CH2:31][CH2:32][OH:33])=[C:28]([F:36])[CH:27]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 230907402-(4-Bromo-2-fluorophenoxy)ethanolHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Product 1

HCID 86698754HCID 86698754, compoundYield 31.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (100 mg, 0.38 mmol) and N,N-dimethylformiminium chloride (97 mg, 0.76 mmol) in DMF (3 mL) and dioxane (0.6 mL) was stirred at room temperature for 30 min. Potassium carbonate (2 mL, 4 mmol, 2 N) was added to the mixture. Then 2-(4-bromo-2-fluorophenoxy)ethanol (89 mg, 0.38 mmol) and Pd(dppf)Cl2 (20 mg, 0.03 mmol) was added to the reaction. The mixture was degassed by passing nitrogen through the solution for 5 min. and stirred at 80° C. for 2 hrs. The reaction was cooled and concentrated. The residue was dissolved with EtOAc (100 mL), washed with water (30 mL), saturated ammonium chloride (30 mL), brine (30 mL), dried over sodium sulfate and concentrated to afford a crude product. The crude was further purified by silica gel chromatography (PE/EtOAc=20% to 50%) to give the title compound (40 mg, 30% yield) as a light yellow oil. 1H NMR (400 MHz, CD3OD) δ 9.89 (s, 1H), 8.17 (s, 1H), 8.11 (s, 1H), 7.62 (s, 1H), 7.20 (m, 3H), 4.18 (t, 2H), 3.93 (t, 2H).

Workup

  1. customThe mixture was degassed
  2. customfor 5 min.
  3. stirringstirred at 80° C. for 2 hrs
  4. temperatureThe reaction was cooled
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved with EtOAc (100 mL)
  7. washwashed with water (30 mL), saturated ammonium chloride (30 mL), brine (30 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto afford a crude product
  11. customThe crude was further purified by silica gel chromatography (PE/EtOAc=20% to 50%)

Sources & evidence

ORD record
ord-aae9b5e67eeb4412b54f2c266de212f3
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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