Methyl iodide → 2-(4-bromo-1H-indol-3-yl)propanenitrile

HRID 12618Notes

Reaction equation

HRID 12618 reaction equation
O1CCC[CH2:2]1.[Br:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([CH2:23][C:24]#[N:25])=[CH:10][N:11]2C(OC(C)(C)C)=O.C([N-]C(C)C)(C)C.[Li+].CI>O.CO>[Br:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([CH:23]([CH3:2])[C:24]#[N:25])=[CH:10][NH:11]2

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 2724682Lithium diisopropylamideHCID 68692455dimethylethyl 4-bromo-3-(cyanomethyl)-1H-indole-1-carboxylate

Product 1

HCID 686961552-(4-bromo-1H-indol-3-yl)propanenitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a tetrahydrofuran solution (10 mL) of 1, -dimethylethyl 4-bromo-3-(cyanomethyl)-1H-indole-1-carboxylate [CAS registration number 151726-05-5, Organic Letters 2003, 5(19), 3519-3522] (1.0 g), lithium diisopropylamide (2M tetrahydrofuran solution; 3.4 mL) was added dropwise at −78° C. and the mixture was stirred at the same temperature for one hour. To the mixture, methyl iodide (0.5 mL) was added, followed by stirring for one hour. The mixture was gradually heated to room temperature and methanol (2 mL) was added. The mixture was stirred overnight at room temperature and water was added under ice cooling, followed by extraction with ethyl acetate. The organic layer was washed in turn with water and saturated saline, dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=80:20 y 70:30) to obtain the titled compound having the following physical properties (0.35 g).

Workup

  1. stirringby stirring for one hour
  2. stirringThe mixture was stirred overnight at room temperature
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed in turn with water and saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=80:20 y 70:30)

Sources & evidence

ORD record
ord-0c8396c2e311451a90052e3059475ff1
Source dataset
uspto-grants-2010_06
Patent number
US07728023B2

Reaction notes

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