Methyl iodide → Ethyl 6-cyano-1-methyl-1h-indole-2-carboxylate

HRID 2367730Notes

Reaction equation

HRID 2367730 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([C:15]#[N:16])[CH:9]=2)=[O:5])[CH3:2].[H-].[Na+].I[CH3:20]>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:20])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([C:15]#[N:16])[CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 4715002Ethyl 6-cyano-1H-indole-2-carboxylate

Product 1

HCID 66656402Ethyl 6-cyano-1-methyl-1h-indole-2-carboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Treat a solution of 6-cyano-1H-indole-2-carboxylic acid ethyl ester (86 mg, 0.40 mmol) in THF (3 mL) with sodium hydride (60% disp. in mineral oil, 18 mg, 0.44 mmol) under N2. After stirring for 10 min, add iodomethane (68 mg, 0.48 mmol) and stir at rt for 3 h. Quench the reaction with sat. NH4Cl solution and extract several times with EtOAc. Dry the combined organic layers (Na2SO4) and concentrate to give a solid. Purify the crude product by silica gel chromatography (MeOH/DCM: 0% to 10%) to give the desired 6-cyano-1-methyl-1H-indole-2-carboxylic acid ethyl ester in 59% yield (54 mg, 0.24 mmol).

Workup

  1. stirringstir at rt for 3 h
  2. customQuench
  3. customthe reaction with sat. NH4Cl solution
  4. extractionextract several times with EtOAc
  5. dry with materialDry the combined organic layers (Na2SO4)
  6. concentrationconcentrate
  7. customto give a solid
  8. customPurify the crude product by silica gel chromatography (MeOH/DCM: 0% to 10%)

Sources & evidence

ORD record
ord-c12269d96d364b31a0e308e14495f41e
Source dataset
uspto-grants-2014_04
Patent number
US08697911B2

Reaction notes

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