Sodium hydride → HCID 69507192, compound

HRID 1744446Notes

Reaction equation

HRID 1744446 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].C([O:15][C:16](=O)[C:17]([C:29]#[N:30])=[CH:18][C:19]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[CH:20]=1)C>C1COCC1>[CH3:28][O:27][C:21]1[CH:20]=[C:19]([C:18]2[CH:17]([C:29]#[N:30])[C:16](=[O:15])[O:1][C:2]3[C:10]=2[CH:9]=[CH:8][C:7]2=[N:6][CH:5]=[CH:4][C:3]=32)[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 754211H-indol-4-olHCID 2732672HCID 2732672, compound

Product 1

HCID 69507192HCID 69507192, compoundYield 1.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3,5-dimethoxybenzaldehyde (1.35 g, 8.12 mmol) and ethyl cyanoacetate (0.92 ml, 8.1 mmol) in ethanol (10 mL) was added piperidine (0.4 mL, 4 mmol). The mixture was stirred at room temperature for approximately 2 h. A precipitate formed, which was collected by filtration and dried to yield approximately 2.12 g of a white solid, which was used directly in the next step. To a solution of 4-hydroxyindole (250 mg, 1.91 mmol) in THF (10 mL) was added sodium hydride (153 mg, 3.80 mmol, 60%) and the mixture was stirred at room temperature for approximately 10 min. To the mixture was added a solution of 3-(3,5-dimethoxyphenyl)-2-cyano-acrylic acid ethyl ester (500 mg, 1.91 mmol, prepared as described above) in THF (2 mL). The mixture was heated at approximately 60° C. overnight. The solvent was evaporated and the residue was purified by flash column chromatography (silica gel, EtOAc:hexane, 1:2), yielding 7 mg (1.1%) of the title compound. 1H NMR (CDCl3): 8.64 (brs, 1H), 7.35-7.24 (m, 2H), 7.19-7.16 (m, 1H), 7.04 (s, 1H), 6.65-6.59 (m, 3H), 3.85 (s, 6H).

Workup

  1. temperatureThe mixture was heated at approximately 60° C. overnight
  2. customThe solvent was evaporated
  3. customthe residue was purified by flash column chromatography (silica gel, EtOAc:hexane, 1:2)

Sources & evidence

ORD record
ord-017f8aac01d14c03b4854087c6d459f0
Source dataset
uspto-grants-2006_03
Patent number
US07015328B2

Reaction notes

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