Isopropyl iodide → Methyl 1-(1-methylethyl)-7-(methyloxy)-1H-indole-4-carboxylate

HRID 593826Notes

Reaction equation

HRID 593826 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[NH:10][CH:9]=[CH:8][C:7]=2[C:6]([C:12]([O:14][CH3:15])=[O:13])=[CH:5][CH:4]=1.[H-].[Na+].I[CH:19]([CH3:21])[CH3:20]>CN(C=O)C>[CH3:20][CH:19]([N:10]1[C:11]2[C:3]([O:2][CH3:1])=[CH:4][CH:5]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[C:7]=2[CH:8]=[CH:9]1)[CH3:21]

Participants

5

Reactant 3

HCID 6362Isopropyl iodide2×HCID 24758Sodium hydride2×HCID 11020003Methyl 7-methoxy-1H-indole-4-carboxylate

Product 1

HCID 67468655Methyl 1-(1-methylethyl)-7-(methyloxy)-1H-indole-4-carboxylateYield 94.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (ice/water bath) solution of methyl 7-(methyloxy)-1H-indole-4-carboxylate (350 mg, 1.706 mmol) in DMF (20 mL) was added sodium hydride (56.0 mg, 2.217 mmol). After 10 minutes added 2-iodopropane (0.188 mL, 1.876 mmol). The reaction was stirred at RT for 1 h, followed by heating at 50° C. for 2 h. The reaction was then cooled in an ice water bath and more sodium hydride (56.0 mg, 2.217 mmol) and 2-iodopropane (0.188 mL, 1.876 mmol) were added. The reaction was heated at 50° C. for 3 h, at which time it was concentrated. The residue was dissolved in DCM and washed with water and brine, dried over MgSO4, filtered and concentrated to give 400 mg of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.49 (d, 6H), 3.95 (s, 3H), 4.01 (s, 3H), 5.46 (dt, J=13.39, 6.69 Hz, 1H), 6.66 (d, J=8.34 Hz, 1H), 7.15 (d, J=3.03 Hz, 1H), 7.34 (d, J=3.28 Hz, 1H), 7.87 (d, J=8.34 Hz, 1H). MS(ES) [M+H]+248.2.

Workup

  1. temperatureby heating at 50° C. for 2 h
  2. temperatureThe reaction was then cooled in an ice water bath
  3. temperatureThe reaction was heated at 50° C. for 3 h, at which time it
  4. concentrationwas concentrated
  5. dissolutionThe residue was dissolved in DCM
  6. washwashed with water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d5edd2b1f1844113af1e2499decd8f6f
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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