Methyl iodide → (5-Fluoro-1H-indol-3-yl)acetonitrile

HRID 894319Notes

Reaction equation

HRID 894319 reaction equation
CN([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:14])[CH:12]=2)[NH:7][CH:6]=1)C.[C-:15]#[N:16].[K+].CI>CO.O>[F:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:4][C:15]#[N:16]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 9032Potassium CyanideHCID 95765-Fluorogramine2×

Product 1

HCID 12883709(5-Fluoro-1H-indol-3-yl)acetonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 38 g of 3-dimethylaminomethyl-5-fluoroindole (0.198 mole; cf. Hoffman et al. J. Heterocyclic Chem. 2, 298 [1965]; of the 5-fluorogramine therein) in 500 ml of methanol was prepared. Then a solution of 25.7 g of KCN (0.396 mole) in 50 ml of water was added, with stirring. The stirred mixture was cooled to 20° C. and 34.6 ml of methyl iodide (0.556 mole) was added over a 20 minute period. The mixture was then stirred about 20° C. for 16 hours. The solvent was removed by evaporation and the residue was partitioned between ether and water. The ether portion was washed with water, 5% HCl, saturated NaHCO3 solution, water, and brine, dried over MgSO4 and evaporated to leave a liquid residue. This residue was distilled at reduced pressure in a Kugelrohr apparatus. The fraction distilling at 134°-140° C. and 0.3 to 0.1 Torr was collected and crystallized from ethyl acetate-petroleum ether, mp. 58°-59°, yield 5.3 g (44% theory).

Workup

  1. stirringThe mixture was then stirred about 20° C. for 16 hours
  2. customThe solvent was removed by evaporation
  3. customthe residue was partitioned between ether and water
  4. washThe ether portion was washed with water, 5% HCl, saturated NaHCO3 solution, water, and brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customto leave a liquid residue
  8. distillationThis residue was distilled at reduced pressure in a Kugelrohr apparatus
  9. distillationThe fraction distilling at 134°-140° C.
  10. custom0.3 to 0.1 Torr was collected
  11. customcrystallized from ethyl acetate-petroleum ether, mp. 58°-59°, yield 5.3 g (44% theory)

Sources & evidence

ORD record
ord-37ec23e3924a4e26a5d75a5c87fcd2ed
Source dataset
uspto-grants-1981_08
Patent number
US04283410

Reaction notes

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