Ethyl Acetate → Methyl 4-(5-cyanoindol-3-ylmethyl)-3-methoxybenzoate

HRID 728038Notes

Reaction equation

HRID 728038 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)#[N:2].Br[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[O:24][CH3:25].C(OCC)(=O)C>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[O:24][CH3:25])#[N:2]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 27513Indole-5-carbonitrileHCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoate

Product 1

HCID 14882553Methyl 4-(5-cyanoindol-3-ylmethyl)-3-methoxybenzoateYield 53%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 5-cyanoindole (10 g) and freshly prepared silver carbonate on diatomaceous earth (40.66 g) was stirred and heated under reflux in toluene (100 ml) for 18 h, under an atmosphere of nitrogen. The mixture was cooled to room temperature, methyl 4-bromomethyl-3-methoxybenzoate (22.7 g) added, and stirring continued for 4 h. Ethyl acetate (200 ml) was added, the mixture filtered through diatomaceous earth, the filter pad washed with ethyl acetate and the filtrate evaporated. The dark oil obtained was purified by flash chromatography, eluting with 45:45:10 hexane:methylene chloride:ethyl acetate, to give a foam which was crystallized from toluene to give methyl 4-(5-cyanoindol-3-ylmethyl)-3-methoxybenzoate (11.8 g, 53%) as white crystals; mp 148-149°; partial NMR (250 MHz, DMSO-d6): 3.83(s, 3H, OCH3), 3.91(s, 3H, OCH3), 4.08(s, 2H, ArCH2Ar'), 8.00(s, 1H, H4 -indole), 11.49(br s, 1H, H1 -indole).

Workup

  1. temperatureheated
  2. stirringstirring
  3. filtrationthe mixture filtered through diatomaceous earth
  4. washthe filter pad washed with ethyl acetate
  5. customthe filtrate evaporated
  6. customThe dark oil obtained
  7. customwas purified by flash chromatography
  8. washeluting with 45:45:10 hexane
  9. custommethylene chloride:ethyl acetate, to give a foam which
  10. customwas crystallized from toluene

Sources & evidence

ORD record
ord-3e578699a95448e2b574cd4c81b4180a
Source dataset
uspto-grants-1991_09
Patent number
US05047402

Reaction notes

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