Toluene → (1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrile

HRID 644055Notes

Reaction equation

HRID 644055 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19]([OH:21])=O)=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[Cu][C:29]#[N:30].C1(C)C=CC=CC=1>ClCCl.C(#N)C>[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19](=[O:21])[C:29]#[N:30])=[CH:9]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 65578Oxalyl chlorideHCID 686950531-(Cyclohexylmethyl)-7-methoxyindole-3-carboxylic acidHCID 178418546HCID 178418546, compound2×

Product 1

HCID 86613200(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrileYield 84.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-cyclohexylmethyl-7-methoxy-1H-indole-3-carboxylic acid (5 g, 17.4 mmol) in dichloromethane (100 ml) was added oxalyl chloride (3.04 ml, 34.8 mmol) and the resulting solution stirred overnight. Excess solvent and reagent were then removed by evaporation. To the resulting residue was added copper (I) cyanide (6.2 g, 69.6 mmol), toluene (200 ml) and acetonitrile (10 ml) and the resulting reaction mixture heated at reflux for 7 hours. A further portion of copper (I) cyanide (1.6 g, 17.9 mmol) was then added and the reaction mixture heated at reflux overnight. The reaction mixture was cooled and filtered through a pad of dicalite. The dicalite was washed with acetonitrile and the combined filtrate evaporated to leave a red solid. The solid was purified by flash column chromatography eluting with 50% (v/v) dichloromethane in heptane to afford (1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrile (4.7 g, 14.7 mmol).

Workup

  1. customExcess solvent and reagent were then removed by evaporation
  2. customthe resulting reaction mixture
  3. temperatureheated
  4. temperatureat reflux for 7 hours
  5. temperaturethe reaction mixture heated
  6. temperatureat reflux overnight
  7. temperatureThe reaction mixture was cooled
  8. filtrationfiltered through a pad of dicalite
  9. washThe dicalite was washed with acetonitrile
  10. customthe combined filtrate evaporated
  11. customto leave a red solid
  12. customThe solid was purified by flash column chromatography
  13. washeluting with 50% (v/v) dichloromethane in heptane

Sources & evidence

ORD record
ord-bc5c49eb32b244dc8b15bf58fc0652c9
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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