Tetrahydrofuran → Ethyl 1-[2-(acetylamino)ethyl]-6-methoxy-1H-indole-2-carboxylate

HRID 1675339Notes

Reaction equation

HRID 1675339 reaction equation
[C:1]([CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]1[C:15]([O:17][CH2:18][CH3:19])=[O:16])#[N:2].[O:20]1CC[CH2:22][CH2:21]1>[Ni]>[C:21]([NH:2][CH2:1][CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]1[C:15]([O:17][CH2:18][CH3:19])=[O:16])(=[O:20])[CH3:22]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 67331182Ethyl 1-(cyanomethyl)-6-methoxy-1H-indole-2-carboxylate

Product 1

HCID 67330577Ethyl 1-[2-(acetylamino)ethyl]-6-methoxy-1H-indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

Dissolve 0.34 g of the compound obtained in Step A in 10 ml of tetrahydrofuran and add a catalytic amount of Raney nickel and hydrogenate the reaction (10 bars) at ambient temperature for 24 hours. Filter over Celite and then evaporate. Take up the residue in 10 ml of tetrahydrofuran in the presence of 0.16 ml of triethylamine and, at 0° C. under argon, add dropwise 0.15 ml of acetic anhydride. Stir the reaction at ambient temperature for 22 hours. Evaporate, and take up the residue in ethyl acetate. Wash the organic phase with saturated aqueous sodium hydrogen carbonate solution and then with saturated aqueous sodium chloride solution and subsequently dry over sodium sulfate. Filter and evaporate in vacuo, and then purify the compound by column chromatography on silica gel using ethyl acetate as eluant. The title compound is isolated in the form of a white solid.

Workup

  1. customthe reaction (10 bars) at ambient temperature for 24 hours
  2. filtrationFilter over Celite
  3. customevaporate
  4. additionat 0° C. under argon, add dropwise 0.15 ml of acetic anhydride
  5. customthe reaction at ambient temperature for 22 hours
  6. customEvaporate
  7. washWash the organic phase with saturated aqueous sodium hydrogen carbonate solution
  8. dry with materialwith saturated aqueous sodium chloride solution and subsequently dry over sodium sulfate
  9. filtrationFilter
  10. customevaporate in vacuo
  11. custompurify the compound by column chromatography on silica gel

Sources & evidence

ORD record
ord-6bac557e352845a081e4cd4ec98cdd88
Source dataset
uspto-grants-2011_08
Patent number
US08003682B2

Reaction notes

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