Water → 1-Acetyl-2,3-dimethylindole-5-carboxylic acid ethyl ester

HRID 280616Notes

Reaction equation

HRID 280616 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([CH3:17])=[C:11]2[CH3:18])=[O:7])[CH3:4].[C:19](Cl)(=[O:21])[CH3:20].O>CN(C)C=O>[CH2:3]([O:5][C:6]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([C:19](=[O:21])[CH3:20])[C:12]([CH3:17])=[C:11]2[CH3:18])=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 24758Sodium hydrideHCID 612460Ethyl 2,3-dimethyl-1H-indole-5-carboxylate

Product 1

HCID 136630551-Acetyl-2,3-dimethylindole-5-carboxylic acid ethyl esterYield 29.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.8 g of 50% dispersion in mineral oil) was added portionwise to a stirred solution of 2,3-dimethylindole-5-carboxylic acid ethyl ester (3.50 g) in dry N,N-dimethylformamide (25 ml) and the mixture was stirred at room temperature for 30 minutes and then cooled to 0°. A solution of acetyl chloride (1.27 g) in dry N,N-dimethylformamide (2.5 ml) was added dropwise with stirring over 2 minutes. The resulting mixture was stirred at room temperature for 3 hours and then poured into water. The mixture was extracted several times with ethyl acetate and the combined extracts were washed well with water and dried (Na2SO4). Evaporation of the solvent gave an oil which was chromatographed on silica gel. Elution with chloroform first gave mineral oil followed by product. Evaporation of the product-containing fractions gave a solid which was crystallised from ethyl acetate/petrol (b.p. 60°-80°) to give 1-acetyl-2,3-dimethylindole-5-carboxylic acid ethyl ester (1.22 g), m.p. 98°-101°.

Workup

  1. temperaturecooled to 0°
  2. stirringwith stirring over 2 minutes
  3. stirringThe resulting mixture was stirred at room temperature for 3 hours
  4. extractionThe mixture was extracted several times with ethyl acetate
  5. washthe combined extracts were washed well with water
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the solvent
  8. customgave an oil which
  9. customwas chromatographed on silica gel
  10. washElution with chloroform first gave mineral oil
  11. customEvaporation of the product-containing fractions
  12. customgave a solid which
  13. customwas crystallised from ethyl acetate/petrol (b.p. 60°-80°)

Sources & evidence

ORD record
ord-d3533330ccf04d609f0f856bf7438d58
Source dataset
uspto-grants-1986_05
Patent number
US04590200

Reaction notes

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