Ethanol → HCID 70896040, compound

HRID 2403671Notes

Reaction equation

HRID 2403671 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]#[N:12].[C:13]([O-:16])(=[O:15])C.[Na+].[CH2:18](O)[CH3:19]>>[C:11]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:13]([O:16][CH2:18][CH3:19])=[O:15])[CH:3]=2)[NH:7][CH:6]=1)#[N:12]

Participants

4

Reactant 3

HCID 702EthanolHCID 517045Sodium AcetateHCID 36233545-Bromo-3-cyanoindole

Product 1

HCID 70896040HCID 70896040, compoundYield 41%

Conditions

Temperature
70 °C

Procedure

To a solution of 5-bromo-1H-indole-3-carbonitrile (2.61 g, 11.8 mmol) in ethanol (50 mL) in a 500 mL Parr bottle was added sodium acetate (2.90 g, 35.6 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (1.93 g, 2.36 mmol). The reaction mixture was evacuated and back filled with nitrogen three times. The reaction vessel was then pressurized with 25 psi carbon monoxide. The reaction was heated to 70° C. and when the desired temperature was reached the pressure of the vessel was increased to 40 psi. The reaction was agitated at 70° C. for 24 hours. The mixture was filtered through Celite, rinsing with ethanol. The filtrate was concentrated under reduced pressure and then diluted with dichloromethane. The mixture was filtered to remove the insoluble solids. The filtrate was concentrated and purified by flash column chromatography (20-80% ethyl acetate/heptanes). The resulting solid was triturated with dichloromethane and a small amount of heptanes to give ethyl 3-cyano-1H-indole-5-carboxylate (1.05 g, 41%) 1H NMR (400 MHz, DMSO-d6, δ): 12.54 (br. s., 1 H), 8.41 (d, J=2.7 Hz, 1 H), 8.25 (d, J=1.6 Hz, 1 H), 7.89 (dd, J=8.6, 1.6 Hz, 1 H), 7.66 (dd, J=8.6, 0.6 Hz, 1 H), 4.34 (q, J=7.0 Hz, 2 H), 1.35 (t, J=7.1 Hz, 3 H).

Workup

  1. customThe reaction mixture was evacuated
  2. additionback filled with nitrogen three times
  3. temperaturewas increased to 40 psi
  4. filtrationThe mixture was filtered through Celite
  5. washrinsing with ethanol
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. additiondiluted with dichloromethane
  8. filtrationThe mixture was filtered
  9. customto remove the insoluble solids
  10. concentrationThe filtrate was concentrated
  11. custompurified by flash column chromatography (20-80% ethyl acetate/heptanes)
  12. customThe resulting solid was triturated with dichloromethane

Sources & evidence

ORD record
ord-e83c817d4c1745d0bb03b4abab773798
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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