Triethylamine → 2-(5-bromo-1H-indol-3-yl)propanenitrile

HRID 402307Notes

Reaction equation

HRID 402307 reaction equation
CS(Cl)(=O)=O.[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH2:16][CH2:17]O.[CH2:19]([N:21](CC)CC)C.[OH-].[Na+].[C-]#N.[K+]>C(Cl)Cl>[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH:16]([CH3:17])[C:19]#[N:21]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 9032Potassium CyanideHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 1229565-Bromo-1H-indole-3-ethanol

Product 1

HCID 681530372-(5-bromo-1H-indol-3-yl)propanenitrileYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The method of Bascop, S. I.; Laronze, J. Y.; Sapi, J. Synthetis of 2-aminopropyle-3-indole-acetic(propionic) acid derivatives. ARKIVOC 2003, 46-61, was followed. Methane sulphonyl chloride (MsCl, 0.55 mL, 2 equiv) was added to a stirred solution of 13 (3.2 mmol, 1 equiv), triethylamine (0.9 mL, 2 equiv) and anhydrous CH2Cl2 (20 mL) maintained at 0° C. The reaction mixture was then stirred for 30 min at 0° C. under N2, after which it was treated with 2M NaOH and extracted with CH2Cl2. The combined organic layer was washed with water, dried (anhydrous Na2SO4) and evaporated to dryness under reduced pressure. The residue was dissolved in anhydrous DMSO (20 mL), KCN (3.25 mmol, 3 equiv) was added and the reaction mixture was heated at 100° C. in an oil bath for 1 h. It was diluted with a water-ice mixture, extracted with chloroform, the combined organic layer was washed with water, dried (anhydrous Na2SO4), and evaporated to dryness under reduced pressure. The residue was purified by column chromatography with CHCl3 as eluting solvent and 14 was obtained. Yield: 75%; 1H NMR (300 MHz, DMSO-d6): δ 2.78 (t, J=15 Hz, 2 H), 3.58 (t, J=12 Hz, 2 H), 7.14-7.17 (m, 2 H), 7.20 (d, J=27 Hz, 1 H), 7.68 (s, 1 H), 11.01 (s, 1 H); MS (APCI): m/z 261.3 [M+H]+.

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined organic layer was washed with water
  3. dry with materialdried (anhydrous Na2SO4)
  4. customevaporated to dryness under reduced pressure
  5. dissolutionThe residue was dissolved in anhydrous DMSO (20 mL)
  6. temperaturethe reaction mixture was heated at 100° C. in an oil bath for 1 h
  7. extractionextracted with chloroform
  8. washthe combined organic layer was washed with water
  9. dry with materialdried (anhydrous Na2SO4)
  10. customevaporated to dryness under reduced pressure
  11. customThe residue was purified by column chromatography with CHCl3
  12. washas eluting solvent
  13. custom14 was obtained

Sources & evidence

ORD record
ord-180abff339ea4883a1b49cae311ccf7b
Source dataset
uspto-grants-2014_06
Patent number
US08742100B2

Reaction notes

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