Methyl iodide → 2-(6-methoxy-1H-indol-3-yl)acetonitrile

HRID 1503121Notes

Reaction equation

HRID 1503121 reaction equation
CN([CH2:4][C:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][CH3:15])=[CH:13][C:8]=2[NH:7][CH:6]=1)C.CI.[Si]([C:22]#[N:23])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1(C)C=CC=CC=1.ClCCl>[CH3:15][O:14][C:12]1[CH:13]=[C:8]2[C:9]([C:5]([CH2:4][C:22]#[N:23])=[CH:6][NH:7]2)=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 82115Trimethylsilyl cyanideHCID 2724141Tetrabutylammonium FluorideHCID 43420386-Methoxygramine

Product 1

HCID 7853622-(6-methoxy-1H-indol-3-yl)acetonitrileYield 95.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-methoxygramine (1.0 g, 4.9 mmol, 1.0 eq.) in a mixture of anhydrous dichloromethane (16 mL) and toluene (30 mL) was added, under an argon atmosphere, methyl iodide (610 μL, 9.8 mmol, 2.0 eq.). The mixture was stirred at room temperature for 16 hours and then, concentrated under reduced pressure. To the residue taken up in anhydrous THF (40 mL) were added, under an argon atmosphere, TMSCN (920 μL, 7.3 mmol, 1.5 eq.) and TBAF (14.7 mL, 1M, 14.7 mmol, 3.0 eq.). The mixture was stirred at room temperature for 4 hours and then, concentrated under reduced pressure. The crude was taken up in ethyl acetate and the organic layer was washed with aqueous bicarbonate solution and then dried over MgSO4. The solvent was removed under reduced pressure, and the residue purified by silica gel pad filtration (eluent: EtOAc) to afford (6-methoxy-1H-indol-3-yl)-acetonitrile as a beige powder (0.87 g, 95%). mp: 100° C.

Workup

  1. additionwas added, under an argon atmosphere
  2. concentrationconcentrated under reduced pressure
  3. additionwere added, under an argon atmosphere
  4. stirringThe mixture was stirred at room temperature for 4 hours
  5. concentrationconcentrated under reduced pressure
  6. washthe organic layer was washed with aqueous bicarbonate solution
  7. dry with materialdried over MgSO4
  8. customThe solvent was removed under reduced pressure
  9. filtrationthe residue purified by silica gel pad filtration (eluent: EtOAc)

Sources & evidence

ORD record
ord-fa98db82cb334fc9974d3870fe2af5c4
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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