Methyl iodide → 6-Fluoro-1-methyl-1h-indole

HRID 226015Notes

Reaction equation

HRID 226015 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:14]>CN(C)C=O>[F:1][C:2]1[CH:10]=[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 3512786-Fluoroindole

Product 1

HCID 179553176-Fluoro-1-methyl-1h-indoleYield 48%

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 6-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 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 0.525 g of the title compound, 48% yield. MS, ES=; 1H NMR (DMSO-d6) δ 7.523-7.488 (m, 1H); 7.300-7.292 (m, 2H); 6.852-6.825 (m, 1H); 6.411-6.409 (m, 1H); 3.767 (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-b0659de059bf47408f58036436a26cac
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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