Methyl iodide → methyl 4-methoxy-1-methyl-1H-indole-2-carboxylate

HRID 1920988Notes

Reaction equation

HRID 1920988 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH:7]=[C:8]([C:14]([O:16][CH3:17])=[O:15])[NH:9]2.[CH3:18]I>CCCCCC.CN(C=O)C>[CH3:3][O:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH:7]=[C:8]([C:14]([O:16][CH3:17])=[O:15])[N:9]2[CH3:18]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 688172methyl 4-methoxy-1H-indole-2-carboxylate

Product 1

HCID 4777904methyl 4-methoxy-1-methyl-1H-indole-2-carboxylateYield 96.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

NaH (60% dispersion in mineral oil, 0.3 g, 7.3 mmole) was washed with hexane then suspended in anhydrous DMF (16 mL). The mixture was cooled to 0° C. and methyl 4-methoxy-1H-indol-2-carboxylate (1.0 g, 4.87 mmole) was added. The mixture was stirred under argon for 10 min, then MeI (1.3 mL, 20 mmole) was added, and the thick slurry was stirred at RT for 2.5 hr. The reaction was quenched with 10% NH4Cl (2 mL) and concentrated. The residue was partitioned between H2O and Et2O, and the organic layer was dried over MgSO4 and concentrated to yield the title compound (1.03 g, 96%) as a white solid: MS (ES) m/e 220.2 (M+H)+.

Workup

  1. stirringthe thick slurry was stirred at RT for 2.5 hr
  2. customThe reaction was quenched with 10% NH4Cl (2 mL)
  3. concentrationconcentrated
  4. customThe residue was partitioned between H2O and Et2O
  5. dry with materialthe organic layer was dried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-1c167eefa16f470bb643ce77246de2b4
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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