Methyl iodide → 2-(1-Tert-butoxycarbonylindol-3-yl)propionitrile

HRID 1258047Notes

Reaction equation

HRID 1258047 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]#[N:19])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[CH3:21][Si]([N-][Si](C)(C)C)(C)C.IC>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH:17]([CH3:21])[C:18]#[N:19])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 15378323tert-Butyl 3-(cyanomethyl)-1H-indole-1-carboxylate

Product 1

HCID 252230692-(1-Tert-butoxycarbonylindol-3-yl)propionitrileYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of (1-tert-butoxycarbonyl indol-3-yl)acetonitrile (5.30 g, 20.7 mmol) in THF (20 mL, anhyd) chilled to −78° C. was added dropwise a 1.0M solution of LiHMDS in THF (21 mL, 21 mmol). After 40 min iodomethane (1.3 mL, 21 mmol) was added rapidly, and the reaction mixture was allowed to warm to ambient temperature. After 15 h the reaction was quenched by addition of 0.2N HCl (100 mL) and extracted with Et2O (2×100 mL). The combined extracts were washed with brine, dried (Na2SO4), concentrated and chromatographed (silica gel, 6% EtOAc/Hex) to give the title compound (4.0 g, 71%) as a light yellow oil. 1H-NMR (CDCl3): δ 8.17 (1H, br d), 7.60 (2H, m), 7.37 (1H, br d), 7.30 (1H, app t), 4.10 (1H, q), 1.76 (3H, d), 1.68 (9H, s).

Workup

  1. customAfter 15 h the reaction was quenched by addition of 0.2N HCl (100 mL)
  2. extractionextracted with Et2O (2×100 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customchromatographed (silica gel, 6% EtOAc/Hex)

Sources & evidence

ORD record
ord-01fc16cadcb74d1cb8b8ab1a5e678a30
Source dataset
uspto-grants-2013_06
Patent number
US08466143B2

Reaction notes

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