Indole → 39597-63-2

HRID 1246938Notes

Reaction equation

HRID 1246938 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].I[CH2:13][C:14]([NH2:16])=[O:15]>CN(C=O)C>[N:1]1([CH2:13][C:14]([NH2:16])=[O:15])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 798IndoleHCID 3727IodoacetamideHCID 24758Sodium hydride2×

Product 1

HCID 440825739597-63-2

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of indole (10 g; 0.085 mol) in DMF (50 mL) was added dropwise to an ice cooled suspension of NaH (supplied as 60% dispersion in mineral oil) (4.1 g; 0.10 mol) in DMF (100 mL). The reaction was allowed to warm to room temperature and stirred for 4 hours until all NaH was consumed. A solution of iodoacetamide (18.5 g; 0.1 mol) in DMF (50 mL) was added and the reaction left to stir at room temperature overnight. The DMF was removed in vacuo and the residue dissolved in ethyl acetate (1 L). The organic solution was washed with water until the washings were clear (3×500 mL), brine (500 mL), dried over anhydrous magnesium sulfate and the solvent removed in vacuo. Recrystallisation from ethyl acetate provided intermediate C1 as an off white solid (9.20 g, 62%). m.p. 177–179° C. 1H NMR (500 MHz, DMSO-d6) δ 4.79 (2H, s), 6.44 (1H, dd, J 3.1, 0.7), 7.03 (1H, ddd, J 7.8, 7.8, 0.9), 7.13 (1H, ddd, J 8.2, 8.2, 1.0), 7.24 (1H, br), 7.31 (1H, d, J 3.1), 7.35 (1H, dd, J 8.2, 0.6), 7.50 (1H, br), 7.55 (1H, d, J 7.8).

Workup

  1. temperaturecooled
  2. customwas consumed
  3. waitthe reaction left
  4. customThe DMF was removed in vacuo
  5. dissolutionthe residue dissolved in ethyl acetate (1 L)
  6. washThe organic solution was washed with water until the washings
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent removed in vacuo
  9. customRecrystallisation from ethyl acetate provided intermediate C1 as an off white solid (9.20 g, 62%)

Sources & evidence

ORD record
ord-70cf7dec33b042efaaa0e82769dde74d
Source dataset
uspto-grants-2006_10
Patent number
US07129250B2

Reaction notes

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