Dimethylformamide → 4-Methoxyindole-3-aldehyde

HRID 250199

Reaction equation

HRID 250199 reaction equation
CN(C=O)C.[C:6](Cl)(=[O:10])[C:7](Cl)=O.[CH3:12][O:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1C=[CH:17][NH:18]2>ClC(Cl)C>[CH3:12][O:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[C:7]([CH:6]=[O:10])=[CH:17][NH:18]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 1383634-Methoxy-1H-indole

Product 1

HCID 1462294-Methoxyindole-3-aldehydeYield 96.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

A solution of dry DMF (0.75 g) in 50 ml dichloroethane was cooled to 0° C. and placed under nitrogen. Oxalyl chloride (1.03 g) dissolved in dichloroethane (5 ml) was added dropwise with stirring. The solution was stirred until no more bubbling was observed (about 15-20 m). 4-Methoxyindole (1.0 g, 6.7 mmole) was added to the solution as a solid and the reaction mixture was stirred at room temperature for four hours. The reaction was quenched by careful addition of 10% sodium carbonate solution. The two phase mixture was stirred at room temperature for 2 hours. The layers were separated and the aqueous layer was extracted with methylene chloride, and the combined organic extracts were dried and evaporated to dryness. The crude residue was passed through a short silica gel column, eluting with 3:7 ethyl acetate:hexane to 1:1 ethyl acetate:hexane to yield 1.13 g (95%) of 4-methoxy-1H-indole-3-carbaldehyde.

Workup

  1. additionwas added dropwise
  2. stirringThe solution was stirred until
  3. customno more bubbling
  4. stirringthe reaction mixture was stirred at room temperature for four hours
  5. customThe reaction was quenched by careful addition of 10% sodium carbonate solution
  6. stirringThe two phase mixture was stirred at room temperature for 2 hours
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with methylene chloride
  9. customthe combined organic extracts were dried
  10. customevaporated to dryness
  11. washeluting with 3:7 ethyl acetate

Sources & evidence

ORD record
ord-49570dac9afd4c6fa553e2c3fbddfdf1
Source dataset
uspto-grants-2011_01
Patent number
US07863305B2

Linked notes

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