Water → Methyl 1-(1-methylethyl)-1H-indole-3-carboxylate

HRID 1372691Notes

Reaction equation

HRID 1372691 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[CH:4]1.[CH:16](I)([CH3:18])[CH3:17].O>CN(C=O)C>[CH:16]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[CH:4]1)([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 962WaterHCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 589098Methyl indole-3-carboxylate

Product 1

HCID 10443342Methyl 1-(1-methylethyl)-1H-indole-3-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In DMF (8.0 ml) was suspended sodium hydride (60% in oil, 275.2 mg, 6.881 mmol). To the resulting suspension was added methyl indole-3-carboxylate (401.8 mg, 2.294 mmol) at 0° C. under stirring. After stirring for further 45 minutes at the same temperature, isopropyl iodide (0.34 ml, 3.440 mmol) was added to the reaction mixture. Stirring was then conducted for 1.5 hours at 0° C. and for 7 hours at room temperature. Water was added to the reaction mixture to terminate the reaction, followed by extraction with ethyl acetate. The extract was washed successively with 1N HCl and saturated saline, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from hexane-ethyl acetate (3:1, v/v) eluate fractions, methyl 1-isopropylindole-3-carboxylate (387.6 mg, 78%) was obtained as a light yellow oil.

Workup

  1. additionwas added to the reaction mixture
  2. stirringStirring
  3. customto terminate
  4. customthe reaction
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe extract was washed successively with 1N HCl and saturated saline
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationdistilled under reduced pressure
  9. customto remove the solvent
  10. customThe residue was purified by chromatography on a silica gel column, whereby from hexane-ethyl acetate (3:1

Sources & evidence

ORD record
ord-6f51e8baaa8a47e393f5c62643d31f7e
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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