Carbon Dioxide → 5-iodo-1-methyl-1H-indole

HRID 984491

Reaction equation

HRID 984491 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].IC.[C:15](=O)=O>C1COCC1.CCCCCC.CCOCC>[CH3:15][N:7]1[C:8]2[C:4](=[CH:3][C:2]([I:1])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 27823135-Iodo-1H-indole

Product 1

HCID 113228355-iodo-1-methyl-1H-indole

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 5-iodoindole (75 g, 0.31 mol) in dry THF (750 mL), at −78° C. was added sodium hydride (60% in mineral oil, 14.85 g, 0.37 mol) in one portion. The suspension was stirred at −78° C. for 1 hour after which iodomethane (28.8 mL, 0.46 mol) was added. The reaction mixture was stirred overnight with a slow elevation of temperature to room temperature (no more dry ice was added). Ether (600 mL) and hexane (1.2 L) were added and the mixture was washed with brine (1.6 L) and water (1.5 L), dried over Na2SO4 and filtered. The solution was concentrated and the residual brown solid was recrystallized from hexane to give the title compound (66 g). The impure fraction from the mother liquor was flash chromatographed (8% EtOAc in hexane) to give an additional quantity of desired product (12.5 g, combined yield of 99%). MS (DCI/NH3) m/e 258 (M+H)+.

Workup

  1. additionwas added
  2. additionwas added)
  3. washthe mixture was washed with brine (1.6 L) and water (1.5 L)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe solution was concentrated
  7. customthe residual brown solid was recrystallized from hexane

Sources & evidence

ORD record
ord-5ed9a02dfa824f8b99de2715a2e404ae
Source dataset
uspto-grants-2005_03
Patent number
US06867203B2

Linked notes

Loading…