tert-Butanol → (1H-Indol-7-yl)acetonitrile

HRID 2215836Notes

Reaction equation

HRID 2215836 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[CH:10]=O)[CH:3]=[CH:2]1.[Li][C:13]#[N:14].P(C#N)(OCC)(OCC)=O.C(O)(C)(C)C>C1COCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[CH2:10][C:13]#[N:14])[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 76257Diethyl cyanophosphonateHCID 2734629Indole-7-carboxaldehydeHCID 178506913HCID 178506913, compound

Product 1

HCID 21949987(1H-Indol-7-yl)acetonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 7-indolecarboxaldehyde (1.0 g, 6.90 mmol) and LiCN 1.5THF (72.5 mg, 0.69 mmol) in 50 ml THF, was added (EtO)2P(O)CN (1.36 ml) at 0° C. The reaction was stirred at rt overnight, and then t-butanol (0.79 ml) was added. The mixture was cannulated into a flask containing an 0.1 M solution of SmI2 in THF (159 ml). Additional SMI2 (10 mol %) was added until no color change was observed. The mixture was stirred for 30 min, and then concentrated and the residue poured into ethyl acetate. The organic layer was washed with 1.0 N HCl, saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by flash chromatography with Hexane:Ethyl acetate=2:1, to give (1H-Indol-7-yl)-acetonitrile as white solid, (300 mg, 30%). MS (m/z) 157.0 (M++1), 155.0 (M+−1). 1HNMR (DMSO) 11.26 (s, 1H), 7.50 (d, J=6.0 Hz, 1H), 7.39 (m, 1H), 7.06 (d, J=5.4 Hz, 1H), 6.97 (dd, J=5.4 Hz, 1H), 6.46 (m, 1H), 4.18 (s, 2H).

Workup

  1. customThe mixture was cannulated into a flask
  2. additionAdditional SMI2 (10 mol %) was added until no color change
  3. stirringThe mixture was stirred for 30 min
  4. concentrationconcentrated
  5. additionthe residue poured into ethyl acetate
  6. washThe organic layer was washed with 1.0 N HCl, saturated aqueous NaHCO3 and brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography with Hexane

Sources & evidence

ORD record
ord-64e7bdf8de9e4501b3a487742e80b01b
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

Loading…