Dimethylformamide → Ethyl 4-cyano-1-cyclopropyl-1H-indole-6-carboxylate

HRID 1096973Notes

Reaction equation

HRID 1096973 reaction equation
[CH:1]1([N:4]2[C:12]3[C:7](=[C:8](OS(C(F)(F)F)(=O)=O)[CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=3)[CH:6]=[CH:5]2)[CH2:3][CH2:2]1.[CH3:26][N:27](C=O)C>[C-]#N.[Zn+2].[C-]#N>[C:26]([C:8]1[CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=[C:12]2[C:7]=1[CH:6]=[CH:5][N:4]2[CH:1]1[CH2:3][CH2:2]1)#[N:27]

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 57930899HCID 57930899, compound

Product 1

HCID 57930989Ethyl 4-cyano-1-cyclopropyl-1H-indole-6-carboxylate

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
90 °C

Procedure

In a 300-mL egg plant-type flask, tetrakistriphenylphosphine palladium (2.31 g, 2.0 mmol) was added to a DMF (50 mL) solution of ethyl 1-cyclopropyl-4-{[(trifluoromethyl)sulfonyl]oxy}-1H-indole-6-carboxylate (7.54 g, 20 mmol) and zinc cyanide (4.70 g, 40 mmol), then purged with nitrogen, and stirred at 90° C. for 1.5 hours. After left cooled, this was diluted with ethyl acetate (100 mL), and aqueous 25% ammonia (50 mL) and water (50 mL) were added thereto, stirred at room temperature for 30 minutes, extracted with ethyl acetate, and washed with water and saturated saline water in that order. The reaction solution was dried with sodium sulfate, filtered, concentrated, and purified through silica gel column chromatography (Biotage [SiO2, 40+M]) with a hexane/ethyl acetate developer system to obtain the title compound as a yellow solid.

Workup

  1. custompurged with nitrogen
  2. waitAfter left
  3. temperaturecooled
  4. additionthis was diluted with ethyl acetate (100 mL), and aqueous 25% ammonia (50 mL) and water (50 mL)
  5. additionwere added
  6. stirringstirred at room temperature for 30 minutes
  7. extractionextracted with ethyl acetate
  8. washwashed with water and saturated saline water in that order
  9. dry with materialThe reaction solution was dried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified through silica gel column chromatography (Biotage [SiO2, 40+M]) with a hexane/ethyl acetate developer system

Sources & evidence

ORD record
ord-cb0af7c66f1643f28fb718fc76de3e98
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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