Methyl iodide → Methyl 1-methyl-1H-indole-4-carboxylate

HRID 2370310Notes

Reaction equation

HRID 2370310 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[C:6]=2[CH:5]=[CH:4]1.I[CH3:17]>CN(C=O)C>[CH3:17][N:3]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[C:6]=2[CH:5]=[CH:4]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2733668methyl 1H-indole-4-carboxylate

Product 1

HCID 12396110Methyl 1-methyl-1H-indole-4-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirring suspension of sodium hydride (60% dispersion in mineral oil, 9.90 g, 248 mmol) in DMF (150 mL) was slowly added a solution of methyl indole-4-carboxylate (10.0 g, 62.1 mmol) in DMF (100 mL) at room temperature under an atmosphere of nitrogen. The mixture stirred for 30 minutes, then iodomethane (15.4 mL, 248 mmol) was added and the mixture continued to stir at room temperature for an additional 16 hours. The mixture was quenched with a saturated solution of ammonium chloride (500 mL) and the aqueous mixture was extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with water (4×300 mL) and brine (200 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification of the resulting residue by column chromatography (0% to 30% ethyl acetate in hexanes) afforded methyl 1-methyl-1H-indole-4-carboxylate (Ala, 10.56 g, 90%) as an oil, which crystallized upon standing: 1H NMR (500 MHz, CDCl3) δ 7.91 (d, J=1.7 Hz, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.21 (m, 1H), 7.14 (s, 1H), 7.09 (s, 1H), 3.96 (s, 3H), 3.75 (s, 3H); MS (ESI+) m/z 190 (M+H).

Workup

  1. stirringto stir at room temperature for an additional 16 hours
  2. customThe mixture was quenched with a saturated solution of ammonium chloride (500 mL)
  3. extractionthe aqueous mixture was extracted with ethyl acetate (3×300 mL)
  4. washThe combined organic layers were washed with water (4×300 mL) and brine (200 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the resulting residue by column chromatography (0% to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6eae6a116d9e4689a87e5920283b3f39
Source dataset
uspto-grants-2014_04
Patent number
US08710047B2

Reaction notes

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