Water → 5-Chloroindole

HRID 654478Notes

Reaction equation

HRID 654478 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2.Br[CH2:14][C:15]([O:17]CC)=[O:16].O>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:14][C:15]([OH:17])=[O:16])[CH:8]=[CH:7]2.[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2

Participants

7

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 871105-Chloroindole

Product 2

HCID 871105-ChloroindoleHCID 19887638HCID 19887638, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH 60% dispersion in oil (1.52 g, 38 mmol) in DMF (50 mL) at r.t. there was added, in portions, 5-chloroindole (5.0 g, 33 mol) and the mixture was stirred for 30 minutes. There was added ethyl bromoacetate (7.44 g, 44 mmol) and the mixture was stirred for a further 5 hours. H2O (200 mL) was added and the mixture was extracted with Et2O. These extracts were washed with H2O, dried over MgSO4 and evaporated to a crude oily residue. Chromatography on silica gel, eluting with 5% EtOAc in toluene, afforded the ethyl ester of the title compound contaminated with some 5-chloroindole. This mixture was dissolved in EtOH (100 mL) and 2.5N aqueous NaOH was added (50 mL). The mixture was stirred at r.t. for 2 hours, then concentrated to a small volume. This residue was partitioned between H2O and Et2O, and by acidification of the aqueous fraction with 6N aqueous HCl, the title compound precipitated. The precipitate was filtered, washed with H2O and air-dried to afford the pure title product as a cream-colored solid.

Workup

  1. stirringthe mixture was stirred for a further 5 hours
  2. extractionthe mixture was extracted with Et2O
  3. washThese extracts were washed with H2O
  4. dry with materialdried over MgSO4
  5. customevaporated to a crude oily residue
  6. washChromatography on silica gel, eluting with 5% EtOAc in toluene

Sources & evidence

ORD record
ord-30ce3cbeedd34e92812793a98c871380
Source dataset
uspto-grants-1992_07
Patent number
US05132319

Reaction notes

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