Phosphorus oxychloride → ethyl 3-formyl-1H-indole-2-carboxylate

HRID 2307918Notes

Reaction equation

HRID 2307918 reaction equation
CN([CH:9]=[O:10])C1C=CC=CC=1.P(Cl)(Cl)(Cl)=O.[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17]1[C:25]([O:27][CH2:28][CH3:29])=[O:26].C([O-])(=O)C.[Na+]>ClCCCl>[CH:9]([C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[NH:16][C:17]=1[C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:10]

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 66737N-MethylformanilideHCID 73125Ethyl indole-2-carboxylateHCID 517045Sodium Acetate

Product 1

HCID 5107764ethyl 3-formyl-1H-indole-2-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of N-methylformanilide (2.25 ml) and phosphoryl chloride (1.70 ml) was stirred at ambient temperature for 15 minutes. 1,2-dichloroethane (30 ml) was then added, followed by ethyl indole-2-carboxylate (3 g) and the reaction was heated at reflux for 90 minutes. The reaction mixture was then poured into a mixture of ice/water (200 ml) and sodium acetate (10 g) and extracted with ethyl acetate (2×200 ml). Combined organic phases were evaporated and the crude residue purified by column chromatography using dichloromethane as eluent to give the product as a white solid (2.27 g, 66%); NMR d (CD3SOCD3) 1.40 (t, 3H), 4.42 (q, 2H), 7.25 (m, 1H), 7.40 (m, 1H), 7.55 (m, 1H), 8.20 (m, 1H), 12.77 (s, 1H); M/z (+) 218.3 (MH+).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 90 minutes
  3. extractionextracted with ethyl acetate (2×200 ml)
  4. customCombined organic phases were evaporated
  5. customthe crude residue purified by column chromatography

Sources & evidence

ORD record
ord-66dc72d2204e4064b3569163a607645e
Source dataset
uspto-grants-2004_12
Patent number
US06833387B1

Reaction notes

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