4-Iodophenol → 1-ethyl-2-(4-hydroxyphenyl)-6-methoxy-1H-indole-3-carbonitrile

HRID 502245Notes

Reaction equation

HRID 502245 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]#[N:15])=[CH:4]1)[CH3:2].[Li+].CC([N-]C(C)C)C.B(OC(C)C)(OC(C)C)OC(C)C.I[C:38]1[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.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].CN(C=O)C>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]#[N:15])=[C:4]1[C:38]1[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=1)[CH3:2]

Participants

9

Reactant 5

HCID 108944-IodophenolHCID 11430Potassium CarbonateHCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 116441001-ethyl-6-methoxy-1H-indole-3-carbonitrile

Product 1

HCID 594253351-ethyl-2-(4-hydroxyphenyl)-6-methoxy-1H-indole-3-carbonitrileYield 73%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-ethyl-6-methoxy-1H-indole-3-carbonitrile (2.5 g, 12.5 mmol) in 21 mL of THF is added LDA (23 mL, 22.5 mmol) at −78° C. After warming to 0° C. and stirring for 10 min, the mixture is re-cooled to −78° C. and B(O—iPr)3 (4.35 mL, 18.8 mmol) is added. After the addition, the reaction is allowed to warm to room temperature and stirred for about 1 h. 4-iodophenol (2.89 g, 13.1 mmol), PdCl2(dppf) (510 mg, 0.625 mmol), aqueous K2CO3 (25 mL, 50 mmol) and DMF (42 mL) is added and the reaction mixture is stirred at room temperature overnight. The organic solvent is evaporated under reduced pressure. The residue is washed with water and the mixture is filtered. The filtrate is concentrated to afford crude solid which is purified via column chromatography on silica gel using EtOAc/petroleum ether (1/5 to 2/1) as eluant to yield 73% of 1-ethyl-2-(4-hydroxyphenyl)-6-methoxy-1H-indole-3-carbonitrile.

Workup

  1. temperaturethe mixture is re-cooled to −78° C.
  2. additionAfter the addition
  3. temperatureto warm to room temperature
  4. stirringstirred for about 1 h
  5. stirringthe reaction mixture is stirred at room temperature overnight
  6. customThe organic solvent is evaporated under reduced pressure
  7. washThe residue is washed with water
  8. filtrationthe mixture is filtered
  9. concentrationThe filtrate is concentrated
  10. customto afford crude solid which
  11. customis purified via column chromatography on silica gel

Sources & evidence

ORD record
ord-126fe023160c42deb2fa45374a3db272
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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