Nitrogen → 6-Chloro-5-(4-ethoxyphenyl)-1H-indole

HRID 1054646Notes

Reaction equation

HRID 1054646 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[Na+].[Na+].[CH2:18]([O:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)[CH3:19].N#N>CCO.O.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([CH:5]=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:24]1[CH:25]=[CH:26][C:21]([O:20][CH2:18][CH3:19])=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27343514-Ethoxyphenylboronic acidHCID 144196195-Bromo-6-chloro-1H-indole

Product 1

HCID 866986496-Chloro-5-(4-ethoxyphenyl)-1H-indoleYield 86.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

A solution of 5-bromo-6-chloro-1H-indole (5.92 g, 25.7 mmol), sodium carbonate (5.45 g, 51.4 mmol) and (4-ethoxyphenyl)boronic acid (5.12 g, 30.8 mmol) in EtOH/water/toluene (30 mL, each) was degassed with N2 for 5 minutes, treated with tetrakis(triphenylphosphine)palladium (1.8 g, 16.57 mmol) and degassed for an additional 5 minutes. The reaction mixture was heated to reflux under N2 for 16 hours. The reaction mixture was cooled to room temperature, poured into dilute NH4Cl solution (200 mL), and extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (9-25% EtOAc/petroleum ether) to afford the title compound (6.03 g, 86%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.07 (br, 1 H), 7.50 (s, 1 H), 7.43 (s, 1 H), 7.33 (d, 2 H), 7.15 (m, 1 H), 6.89 (d, 2 H), 6.46 (s, 1 H), 4.02 (q, J=7.00 Hz, 2 H), 1.36 (t, J=7.00 Hz, 3 H).

Workup

  1. customdegassed for an additional 5 minutes
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux under N2 for 16 hours
  4. additionpoured into dilute NH4Cl solution (200 mL)
  5. extractionextracted with CH2Cl2 (3×100 mL)
  6. washThe combined organic layers were washed with brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography (9-25% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-6d47ec217cd745e4b1a1d2e1d0dffc60
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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