Indole → Indole-3-Carboxaldehyde

HRID 1644250Notes

Reaction equation

HRID 1644250 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+].CN([CH:20]=[O:21])C>>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:20]=[O:21])=[CH:2]1

Participants

5

Reactant 4

HCID 798Indole2×HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychloride

Product 1

HCID 10256Indole-3-Carboxaldehyde

Conditions

Temperature
0 °C

Procedure

General procedure (GP-O) for the Vilsmeier formylation of the indole core: Phosphorus oxychloride (1.2 eq) was added slowly to ice-cold DMF and the resulting mixture was stirred at 0° C. for 30 minutes. To this was added a solution of indole A1 (1 eq) in DMF and the mixture continued to stir for 6 hours. The reaction mixture was poured into an ice/water mixture and pH was adjusted to 7 by adding 1 N NaOH. The compound was extracted with ethyl acetate (4×) and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (typical eluents hexanes and ethyl acetate) to afford the desired indole 3-carboxaldehyde D1. The product structure was confirmed by 1H NMR and mass analysis.

Workup

  1. stirringto stir for 6 hours
  2. extractionThe compound was extracted with ethyl acetate (4×)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by silica gel chromatography (typical eluents hexanes and ethyl acetate)

Sources & evidence

ORD record
ord-e1c410df4f264d239647d5b66f67c33f
Source dataset
uspto-grants-2012_02
Patent number
US08124600B2

Reaction notes

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