Dimethylamine → 2-(5-bromo-1H-indol-3-yl)acetonitrile

HRID 2368853Notes

Reaction equation

HRID 2368853 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH2:11]=O.C[NH:14][CH3:15].CI.[C-]#N.[K+]>C(O)(=O)C.O.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:15]#[N:14]

Participants

9

Reactant 5

HCID 674DimethylamineHCID 712FormaldehydeHCID 6328Methyl iodideHCID 9032Potassium CyanideHCID 249055-Bromoindole

Product 1

HCID 138059442-(5-bromo-1H-indol-3-yl)acetonitrileYield 78%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

To a solution of 5-bromoindole (3.0 g, 15.3 mmol, 1.0 eq.) in a mixture of acetic acid (8.0 mL) and water (2.0 mL) were added, at 0° C., formaldehyde (1.5 mL, 37% in H2O, 18.4 mmol, 1.2 eq) and dimethylamine (3.0 mL, 40% in H2O, 27.5 mmol, 1.8 eq). The mixture was stirred at room temperature for 4 hours and then, quenched with ice and 5 M aqueous sodium hydroxide. The mixture was extracted with dichloromethane and then, the organic layer was dried over MgSO4 and partially evaporated. To the solution gramine in dichloromethane (50 mL) were added, under an argon atmosphere, anhydrous toluene (100 mL) and methyl iodide (1.49 mL, 24.5 mmol, 1.6 eq.). The mixture was stirred at room temperature for 36 hours and then, the precipitate was filtered and washed with diethyl ether. To the resulting powder were added water (100 mL) and potassium cyanide (2.9 g, 44.5 mmol, 3.0 eq.). The mixture was stirred at reflux temperature for 1 hour and quenched with a saturated aqueous sodium carbonate solution, after cooling to room temperature. The crude product was extracted with ethyl acetate and then, the organic layer was and dried over MgSO4, filtered through a silica gel pad and concentrated under reduced pressure to afford (5-bromo-1H-indol-3-yl)-acetonitrile as a beige solid (2.8 g, 78%).

Workup

  1. additionwere added, at 0° C.
  2. customquenched with ice and 5 M aqueous sodium hydroxide
  3. extractionThe mixture was extracted with dichloromethane
  4. dry with materialthe organic layer was dried over MgSO4
  5. custompartially evaporated
  6. additionTo the solution gramine in dichloromethane (50 mL) were added, under an argon atmosphere
  7. stirringThe mixture was stirred at room temperature for 36 hours
  8. filtrationthe precipitate was filtered
  9. washwashed with diethyl ether
  10. stirringThe mixture was stirred
  11. temperatureat reflux temperature for 1 hour
  12. customquenched with a saturated aqueous sodium carbonate solution
  13. temperatureafter cooling to room temperature
  14. extractionThe crude product was extracted with ethyl acetate
  15. dry with materialdried over MgSO4
  16. filtrationfiltered through a silica gel pad
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bc93556a2ef6417588132d38c5311f7a
Source dataset
uspto-grants-2014_04
Patent number
US08703808B2

Reaction notes

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