Methyl iodide → 1H-Indole-3-acetonitrile, 4-chloro-6-methoxy-

HRID 489723Notes

Reaction equation

HRID 489723 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]2[C:3]=1[C:4]([CH2:26]N(C)C)=[CH:5][N:6]2[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C.CI.C[Si]([C:36]#[N:37])(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1C=CC=CC=1.O1CCCC1>[Cl:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]2[C:3]=1[C:4]([CH2:26][C:36]#[N:37])=[CH:5][NH:6]2

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 82115Trimethylsilyl cyanideHCID 2724141Tetrabutylammonium FluorideHCID 23589036HCID 23589036, compound

Product 1

HCID 111175861H-Indole-3-acetonitrile, 4-chloro-6-methoxy-

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4-Chloro-6-methoxy-1-tri-tert-butylsilanyl-1H-indol-3-ylmethyl)-dimethyl-amine (0.73 g, 1.85 mmol) in benzene (20 ml) was added methyl iodide (0.52 g, 3.71 mmol). After stirring at ambient temperature for 16 hours, the solvent was removed under reduced pressure. The residue was suspended in anhydrous tetrahydrofuran (10 ml). To this solution was added, sequentially, trimethylsilyl cyanide (0.27 g, 2.78 mmol) and tetrabutylammonium fluoride (1.45 g, 5.56 mmol, 1M in tetrahydrofuran, after which the solution was stirred for an hour. After solvent was removed under reduced pressure, the residue was partitioned between water and ether. The ether extract was dried (anhydrous sodium sulfate) and concentrated under reduced pressure to give (4-Chloro-6-methoxy-1H-indol-3-yl)-acetonitrile as solid (0.41 g, quantitative). 1H NMR (CDCl3) δ: 3.82 (s, 3H), 4.10 (d, 2H, J+1.17 Hz), 6.79 (d, 1H, J=2.07 Hz), 6.79 (d, 1H, J=2.07), 7.16 (m, 1H), 8.11 (b, 1H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionTo this solution was added
  3. customAfter solvent was removed under reduced pressure
  4. customthe residue was partitioned between water and ether
  5. extractionThe ether extract
  6. dry with materialwas dried (anhydrous sodium sulfate)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-56a1381ee57745998f90af7a33e155e0
Source dataset
uspto-grants-2005_12
Patent number
US06979696B2

Reaction notes

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