Methyl iodide → Tert-butyl N-[2-(1-methyl-1H-indol-3-YL)ethyl]carbamate

HRID 1749512Notes

Reaction equation

HRID 1749512 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:2]1.[H-].[Na+].I[CH3:23]>C1COCC1>[CH3:23][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:2]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 691825tert-Butyl (2-(1H-indol-3-yl)ethyl)carbamate

Product 1

HCID 71202127Tert-butyl N-[2-(1-methyl-1H-indol-3-YL)ethyl]carbamateYield 81.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl (2-(1H-Indol-3-yl)ethyl)carbamate (1.50 g, 5.77 mmol) in anhydrous THF (15 mL) was added sodium hydride (300 mg, 7.50 mmol, 60% in mineral oil) at 0° C. under nitrogen. After the resulting reaction mixture was stirred at room temperature for 15 min, iodomethane (982 mg, 6.92 mmol) in THF (5 mL) was added slowly at 0° C. The resulting mixture was stirred at room temperature for 3 h and quenched with saturated aqueous ammonium chloride solution. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The organic solvents were removed under reduced pressure and the residue was purified by silica gel column chromatography (0.6% MeOH in DCM) to afford the title compound (1.29 g, 4.71 mmol, 81% yield) as a brown solid. MS (ESI) m/z 275.1 [M+H]+.

Workup

  1. customAfter the resulting reaction mixture
  2. stirringThe resulting mixture was stirred at room temperature for 3 h
  3. customquenched with saturated aqueous ammonium chloride solution
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe organic solvents were removed under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (0.6% MeOH in DCM)

Sources & evidence

ORD record
ord-9af80a0c6cd2424aa23915ab8c569cc3
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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