Indole → HCID 71683083, compound

HRID 1482777Notes

Reaction equation

HRID 1482777 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[K+].[I:12]I.[H-].[Na+].Br[CH2:17][CH2:18][CH2:19][CH3:20].CN([CH:24]=[O:25])C>CCOC(C)=O.O>[CH2:17]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[O:25][CH3:24])[C:3]([I:12])=[CH:2]1)[CH2:18][CH2:19][CH3:20]

Participants

9

Reactant 6

HCID 798IndoleHCID 807IodineHCID 6228DimethylformamideHCID 8002Butyl bromideHCID 14797Potassium HydroxideHCID 24758Sodium hydride

Product 1

HCID 71683083HCID 71683083, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A round bottom flask containing indole (0.22 mL, 1.70 mmol, 1 equiv) in DMF at R.T. was stirred with KOH (0.10 g, 1.78 mmol, 1.05 equiv) for about 15 min and then treated with I2 (0.44 g, 1.73 mmol, 1.02 equiv). After 30 min, NaH (0.082 g, 2.04 mmol, 1.2 equiv) was added portion-wise. After additional 15 min had passes 1-bromobutane (0.2 mL, 1.87 mmol, 1.1 equiv) was added and the reaction mixture was stirred until completion. Upon completion (TLC monitoring), H2O was added and allowed to stir for 15 min, upon which the mixture was extracted with DCM and the layers were separated. Aqueous layer was washed with DCM (3×) and the combined organic layers were washed with H2O (2×), dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography using EtOAc/n-hexanes to afford 0.449 g (80% yield) as an clear oil with a yellow tint. TLC system: 10% EtOAc/90% n-hexanes. 1H NMR (400 MHz, CDCl3) δ 7.18 (d, J=8.8, 1H), 7.11 (s, 1H), 6.88 (dd, J=2.5, 8.8, 1H), 6.84 (d, J=2.4, 1H), 4.05 (t, J=7.1, 2H), 3.87 (d, J=3.7, 3H), 1.81-1.71 (m, 2H), 1.29 (tt, J=5.2, 10.1, 3H), 0.91 (t, J=7.4, 3H).

Workup

  1. waitAfter additional 15 min had
  2. stirringto stir for 15 min, upon which the mixture
  3. extractionwas extracted with DCM
  4. customthe layers were separated
  5. washAqueous layer was washed with DCM (3×)
  6. washthe combined organic layers were washed with H2O (2×)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by silica gel column chromatography
  10. customto afford 0.449 g (80% yield) as an clear oil with a yellow tint

Sources & evidence

ORD record
ord-592f842879754033b1ff82e98c7db8f4
Source dataset
uspto-grants-2016_08
Patent number
US09416103B2

Reaction notes

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