Methyl iodide → 4-Fluoro-1-methyl-1H-indole

HRID 226013Notes

Reaction equation

HRID 226013 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].I[CH3:14]>CN(C)C=O>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[CH3:14]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 27745024-Fluoroindole

Product 1

HCID 178592214-Fluoro-1-methyl-1H-indoleYield 61.2%

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 4-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 0.675 g of the title compound, 61% yield. MS, ES+=150.1; 1H NMR (DMSO-d6) δ 7.358-7.350 (d, J=3.083, 1H); 7.279-7.258 (d, J=8.368, 1H); 7.126-7.073 (m, 1H); 6.806-6.760 (m, 1H); 6.459-6.452 (d, J=3.083, 1H); 3.787 (s, 1H) 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-c0c9cc8b487b45efb93300d5c8b5a099
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

Loading…