Ethanol → HCID 70896148, compound

HRID 2403665Notes

Reaction equation

HRID 2403665 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]#[N:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[C:13]([O-:16])(=[O:15])C.[Na+].ClCCl.[CH2:21](O)[CH3:22]>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]>[CH2:21]([O:16][C:13]([C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]#[N:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1)=[O:15])[CH3:22]

Participants

6

Reactant 4

HCID 702EthanolHCID 6344DichloromethaneHCID 517045Sodium AcetateHCID 114700676-Bromo-1H-indole-3-carbonitrile

Product 1

HCID 70896148HCID 70896148, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
70 °C

Procedure

To a solution of 6-bromo-1H-indole-3-carbonitrile (328 mg, 1.48 mmol) in ethanol (5 mL) in a 500 mL Parr bottle was added sodium acetate (370 mg, 4.47 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (242 mg, 0.297 mmol). The reaction vessel was purged with nitrogen and evacuated three times and then was filled with 30 psi carbon monoxide. The reaction mixture was heated to 70° C., increasing the pressure within the vessel to 45 psi. The reaction was agitated at 70° C. for 24 hours. The reaction mixture was cooled to room temperature. The mixture was filtered through Celite, rinsing with ethanol. The filtrate was concentrated under reduced pressure and diluted with dichloromethane. The remaining solids were filtered off and the filtrate was concentrated. The residue was purified by flash column chromatography (20-80% ethyl acetate/heptanes) to give 3-cyano-1H-indole-6-carboxylic acid ethyl ester (142 mg, 45%). −APCI (M−H) 213.4; 1H NMR (400 MHz, DMSO-d6, δ): 12.50 (br. s., 1 H), 8.45 (s, 1 H), 8.16 (s, 1 H), 7.82 (dd, J=8.4, 1.4 Hz, 1 H), 7.73 (d, J=8.4 Hz, 1 H), 4.32 (q, J=7.0 Hz, 2 H), 1.33 (t, J=7.0 Hz, 3 H).

Workup

  1. customThe reaction vessel was purged with nitrogen
  2. customevacuated three times
  3. additionwas filled with 30 psi carbon monoxide
  4. temperatureincreasing the pressure within the vessel to 45 psi
  5. temperatureThe reaction mixture was cooled to room temperature
  6. filtrationThe mixture was filtered through Celite
  7. washrinsing with ethanol
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. additiondiluted with dichloromethane
  10. filtrationThe remaining solids were filtered off
  11. concentrationthe filtrate was concentrated
  12. customThe residue was purified by flash column chromatography (20-80% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-cadc3afac83e47c283b7c64aee7d3ec4
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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