Sodium hydride → (Z)-3-[3,5-dimethoxy-4-(2-methoxy-ethoxymethoxy)-phenyl]-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile

HRID 1503114Notes

Reaction equation

HRID 1503114 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH2:14][C:15]#[N:16].[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([O:34][CH3:35])[C:26]=1[O:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])[CH:22]=O>CS(C)=O.COC(C)(C)C.[Cl-].[Na+].O>[CH3:35][O:34][C:25]1[CH:24]=[C:21](/[CH:22]=[C:14](/[C:8]2[C:7]3[C:11](=[CH:12][CH:13]=[C:5]([O:4][CH3:3])[CH:6]=3)[NH:10][CH:9]=2)\[C:15]#[N:16])[CH:20]=[C:19]([O:18][CH3:17])[C:26]=1[O:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 35647832-(5-methoxy-1H-indol-3-yl)acetonitrileHCID 152574973,5-Dimethoxy-4-[(2-methoxyethoxy)methoxy]benzaldehyde

Product 1

HCID 67515332(Z)-3-[3,5-dimethoxy-4-(2-methoxy-ethoxymethoxy)-phenyl]-2-(5-methoxy-1H-indol-3-yl)-acrylonitrileYield 15.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 15413tert-Butyl methyl etherSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of NaH (60 mg, 80%, 2.5 mmol, 1.7 eq.) in DMSO (5 mL) was added, under an argon atmosphere, a solution of (5-methoxy-1H-indol-3-yl)-acetonitrile (331 mg, 1.8 mmol, 1.2 eq.) and 3,5-dimethoxy-4-(2-methoxy-ethoxymethoxy)-benzaldehyde (400 mg, 1.5 mmol, 1.0 eq.) in a mixture of DMSO (7 mL) and tert-butyl methyl ether (7 mL). The reaction apparatus was protected from light and the mixture was stirred at ambient temperature for 3 hours, and then treated with brine (10 mL). The mixture was extracted with ethyl acetate (3×30 mL), and the organic layer was washed with water and saturated aqueous ammonium chloride solution, and then dried over MgSO4. The solvent was removed under reduced pressure and the residue purified by silica gel flash-column chromatography (eluent: heptane/AcOEt, 70:30 to 50:50) to afford (Z)-3-[3,5-dimethoxy-4-(2-methoxy-ethoxymethoxy)-phenyl]-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile as a yellow oil (100 mg) used in the next synthetic step without further purification.

Workup

  1. additionwas added, under an argon atmosphere
  2. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  3. washthe organic layer was washed with water and saturated aqueous ammonium chloride solution
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed under reduced pressure
  6. customthe residue purified by silica gel flash-column chromatography (eluent: heptane/AcOEt, 70:30 to 50:50)

Sources & evidence

ORD record
ord-3d05e33a9fa544e8a4ac73984e4a1a20
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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