Methyl iodide → 6-bromo-7-fluoro-1-methyl-1H-indole

HRID 2042329Notes

Reaction equation

HRID 2042329 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:14]I>C1COCC1>[Br:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH3:14])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 591331976-Bromo-7-fluoro-1H-indole

Product 1

HCID 591330596-bromo-7-fluoro-1-methyl-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-bromo-7-fluoro-1H-indole (470 mg, 2.19 mmol) in THF (7 mL) at −10° C. was added sodium hydride (175 mg, 4.39 mmol, 60% dispersion) and the mixture was stirred at 0° C. for 30 min. Methyl iodide was added at 0° C. and the reaction was allowed to warm to at 10° C. and stirred for 2 h. The reaction was quenched with saturated ammonium chloride and extracted with DCM. The DCM extract was washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography over silica gel eluting with EtOAc/hexane to afford 6-bromo-7-fluoro-1-methyl-1H-indole. 1H NMR (400 MHz, CDCl3) δ=3.95 (d, J=2.00 Hz, 1H), 6.42 (t, J=2.78 Hz, 1H), 6.94 (d, J=3.03 Hz, 1H), 7.09-7.15 (m, 1H) and 7.20 (d, J=8.34 Hz, 1H); MS (ES+): m/z 228.04 [MH+].

Workup

  1. temperatureto warm to at 10° C.
  2. stirringstirred for 2 h
  3. customThe reaction was quenched with saturated ammonium chloride
  4. extractionextracted with DCM
  5. extractionThe DCM extract
  6. washwas washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by column chromatography over silica gel eluting with EtOAc/hexane

Sources & evidence

ORD record
ord-c5ec9dc0e69f4c1da459f5072fc46725
Source dataset
uspto-grants-2013_11
Patent number
US08586546B2

Reaction notes

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