Methyl iodide → 5-fluoro-1-methylindole

HRID 226014Notes

Reaction equation

HRID 226014 reaction equation
[F: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+].I[CH3:14]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:14])[CH:6]=[CH:5]2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 678615-Fluoroindole

Product 1

HCID 47778355-fluoro-1-methylindoleYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In an oven dried, nitrogen purged, 3 neck, 50 mL round bottom flask, 1.00 g (7.40 mmol) of 5-fluoroindole in 10 mL of dry dimethylformamide is reacted with 0.335 g (8.88 mmol) of 60% sodium hydride dispersed in mineral oil at room temperature for 4 h. 0.553 mL (8.88 mmol) of iodomethane is added and the reaction is allowed to stir at room temperature overnight, 15 h. The reaction is quenched with 50 mL of water, extracted 3×50 mL of ethyl acetate, dried (MgSO4), and concentrated. The crude product is purified by chromatography using hexanes:ethyl acetate as a solvent system to obtain 1.00 g of the title compound, 91% yield. MS, ES+218.2 (M+1); 1H NMR (DMSO-d6) δ 7.428-7.366 (m, 1H); 7.293-7.262 (m, 1H); 6.988-6.937 (m, 1H); 6.384-6.376 (m, 1H); 3.766 (s, 3H) ppm.

Workup

  1. customIn an oven dried
  2. customnitrogen purged
  3. additiondispersed in mineral oil at room temperature for 4 h
  4. customThe reaction is quenched with 50 mL of water
  5. extractionextracted 3×50 mL of ethyl acetate
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude product is purified by chromatography

Sources & evidence

ORD record
ord-2885599dff134bf792661174c6234ac7
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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