Dimethylformamide → Methyl 1-methyl-1H-indole-5-carboxylate

HRID 1395882Notes

Reaction equation

HRID 1395882 reaction equation
N1C2[C:4](=[CH:5][C:6]([C:10]([OH:12])=[O:11])=[CH:7][CH:8]=2)[CH:3]=C1.[H-].[Na+].I[CH3:16].[CH3:17][N:18]([CH:20]=O)[CH3:19]>>[CH3:16][O:12][C:10]([C:6]1[CH:5]=[C:4]2[C:19](=[CH:8][CH:7]=1)[N:18]([CH3:17])[CH:20]=[CH:3]2)=[O:11]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 742801H-Indole-5-Carboxylic Acid

Product 1

HCID 10679201Methyl 1-methyl-1H-indole-5-carboxylateYield 93%

Procedure

A solution of 1H-indole-5-carboxylic acid (1.6 g, 10 mmol), sodium hydride (1.2 g, 30 mmol), iodomethane (6.2 mL, 100 mmol) and DMF (40 mL) was stirred and room temperature for 24 hr. The reaction mixture was then quenched with water (5 mL) and diluted with ether (150 mL) and ethyl acetate (50 mL). After washing with aq. NH4Cl (100 mL), water (100 mL) and then brine (100 mL), the organic layer was dried over MgSO4, filtered and concentrated. The remaining material was subjected to flash chromatography (ethyl acetate/hexane 1:4) to provide 1-methyl-1H-indole-5-carboxylic acid methyl ester as a crystalline solid (1.77 g, 93% yield). 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.94 (d, 1H, J=9.0 Hz), 7.34 (d, 1H, J=9.0 Hz), 7.12 (d, 1H, J=2.9 Hz), 6.60 (d, 1H, J=2.9 Hz), 3.94 (s, 3H), 3.83 (s, 3H).

Workup

  1. customThe reaction mixture was then quenched with water (5 mL)
  2. additiondiluted with ether (150 mL) and ethyl acetate (50 mL)
  3. washAfter washing with aq. NH4Cl (100 mL), water (100 mL)
  4. dry with materialbrine (100 mL), the organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f89e4aa913364b80a1682c35f5efeb5f
Source dataset
uspto-grants-2014_12
Patent number
US08900565B2

Reaction notes

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