Triethylamine → HCID 21459900, compound

HRID 864959Notes

Reaction equation

HRID 864959 reaction equation
[C:1]([CH2:3][O:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH3:15])[CH:12]=2)[N:7]([CH3:16])[C:6]=1[C:17]([O:19]C)=O)#[N:2].C(N(CC)CC)C.[H][H].C[O-].[Na+]>O1CCCC1.[Co]>[CH3:15][O:14][C:11]1[CH:10]=[CH:9][C:8]2[N:7]([CH3:16])[C:6]3[C:17](=[O:19])[NH:2][CH2:1][CH2:3][O:4][C:5]=3[C:13]=2[CH:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10942334Sodium MethoxideHCID 21459892HCID 21459892, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 21459900HCID 21459900, compoundYield 33.2%

Reagents, catalysts & solvents 2

HCID 104730CobaltCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 3-(cyanomethoxy)-5-methoxy-1-methyl-1H-indole-2-carboxylate (0.60 g, 2.2 mmol) and triethylamine (0.40 mL, 0.29 g, 2.9 mmol) in 35 mL of tetrahydrofuran in a pressure reaction vessel is treated with Raney cobalt catalyst (0.40 g). The reactor is pressurized with hydrogen (590 psi) and heated at 80° C. for 10 hours. The cooled reaction mixture is filtered and the filtrate evaporated. The oil residue is dissolved in 50 mL of methanol, and sodium methoxide (0.80 g, 15 mmol) is added to the solution. The mixture is heated at reflux for 3 hours, then cooled and evaporated. The residue is distributed between 75 mL of ethyl acetate and 150 mL of brine. The aqueous layer is extracted several times with fresh ethyl acetate. The combined organic layers are washed with brine, dried (anhydrous sodium sulfate) and evaporated. The crude product residue is purified by flash chromatography (silica gel, 5% methanol, in dichloromethane elution) to yield 0.18 g (33%) of product. A sample recrystallized from ethyl acetatehexane has mp 184°-186° C.

Workup

  1. customin a pressure reaction vessel
  2. customThe cooled reaction mixture
  3. filtrationis filtered
  4. customthe filtrate evaporated
  5. dissolutionThe oil residue is dissolved in 50 mL of methanol
  6. temperatureThe mixture is heated
  7. temperatureat reflux for 3 hours
  8. temperaturecooled
  9. customevaporated
  10. extractionThe aqueous layer is extracted several times with fresh ethyl acetate
  11. washThe combined organic layers are washed with brine
  12. dry with materialdried (anhydrous sodium sulfate)
  13. customevaporated
  14. customThe crude product residue is purified by flash chromatography (silica gel, 5% methanol, in dichloromethane elution)

Sources & evidence

ORD record
ord-dbaeb5e9ec4149c5b61c26c700208ff1
Source dataset
uspto-grants-1996_10
Patent number
US05565446

Reaction notes

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