Hydrochloric Acid → HCID 58221535, compound

HRID 1481724Notes

Reaction equation

HRID 1481724 reaction equation
[CH3:1][C:2]([O-:5])(C)[CH3:3].[K+].[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](C(OCC)=O)=[CH:11]2.C(OC)(=O)C=C.Cl>C1C=CC=CC=1.O>[Br:7][C:8]1[CH:16]=[CH:15][C:14]2[N:13]3[CH2:12][CH2:1][C:2](=[O:5])[C:3]3=[CH:11][C:10]=2[CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 259091Ethyl 5-Bromoindole-2-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 58221535HCID 58221535, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of KOtBu (1.0 g, 8.9 mmol) in benzene (20 mL) was added ethyl 5-bromo-1H-indole-2-carboxylate (2.3 g, 8.6 mmol) as a solution in benzene (40 mL) at room temperature. To the resulting white slurry was added methyl acrylate (1.5 mL, 17.1 mmol). The combined solution was heated at 80° C. for 1 h then cooled to room temperature and stirred for an additional 16 h. The reaction mixture was then poured into H2O (100 mL) and the pH was adjusted to 4 with concentrated HCl. The aqueous phase was then extracted with CH2Cl2 (2×200 mL). The combined organic phases were washed with H2O, dried over Na2SO4, filtered and concentrated. The crude residue was then dissolved in EtOH (30 mL), 4M HCl (10 mL) was added, and the mixture was heated to reflux. After stirring at reflux for 3.5 h, the reaction mixture was cooled to room temperature and neutralized with saturated aqueous NaHCO3. The aqueous phase was then washed with Et2O (2×100 mL). The combined organic phase was dried over MgSO4, filtered, and concentrated to afford the title compound as an off white solid (1.3 g, 61%).

Workup

  1. temperaturethen cooled to room temperature
  2. extractionThe aqueous phase was then extracted with CH2Cl2 (2×200 mL)
  3. washThe combined organic phases were washed with H2O
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude residue was then dissolved in EtOH (30 mL)
  8. addition4M HCl (10 mL) was added
  9. temperaturethe mixture was heated to reflux
  10. stirringAfter stirring
  11. temperatureat reflux for 3.5 h
  12. temperaturethe reaction mixture was cooled to room temperature and neutralized with saturated aqueous NaHCO3
  13. washThe aqueous phase was then washed with Et2O (2×100 mL)
  14. dry with materialThe combined organic phase was dried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-619d1c37d5934dacb0d033469daa6725
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

Loading…