Indole → (5-Benzyloxy-indol-1-yl)-acetic acid ethyl ester

HRID 490675Notes

Reaction equation

HRID 490675 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].N1C2C(=CC=CC=2)C=C1.Br[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32]>CN(C=O)C>[CH2:34]([O:33][C:31](=[O:32])[CH2:30][N:14]1[C:15]2[C:11](=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:17][CH:16]=2)[CH:12]=[CH:13]1)[CH3:35]

Participants

6

Reactant 4

HCID 798IndoleHCID 7748Ethyl bromoacetateHCID 146245-BenzyloxyindoleHCID 24758Sodium hydride

Product 1

HCID 59897880(5-Benzyloxy-indol-1-yl)-acetic acid ethyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

5-benzyloxyindole (10.0 g, 44.79 mmol) is dissolved into anhydrous DMF (100 mL) and cooled to 0° C. in an ice water bath. Sodium hydride (2.6 g, 67.18 mmol) is dissolved into anhydrous DMF (100 mL), then slowly added to the indole solution using an addition funnel. The reaction is allowed to stir at 0° C. for 1 h., then the ice bath is removed and the solution is allowed to warm slowly to room temperature. The solution is then cooled back down to 0° C. and ethyl bromoacetate (11.2 g, 67.18 mmol) is then added in one portion. The reaction is allowed to stir at 0° C. for 1 h., then the ice bath is removed and the solution is allowed to warm slowly to room temperature. Upon completion, the reaction is quenched carefully using water, then diluted with EtOAc (300 mL). Brine (100 mL) is added and the two layers are separated in a separatory funnel. The organic layer is rinsed with water (2×75 mL) and then dried over anhydrous magnesium sulfate. The organic layer is then concentrated and purified using flash column chromatography (5% EtOAc/Hexanes) to yield 11.86 g (86%) of (5-Benzyloxy-indol-1-yl)-acetic acid ethyl ester.

Workup

  1. customthe ice bath is removed
  2. temperatureto warm slowly to room temperature
  3. additionis then added in one portion
  4. stirringto stir at 0° C. for 1 h.
  5. customthe ice bath is removed
  6. temperatureto warm slowly to room temperature
  7. customUpon completion, the reaction is quenched carefully using water
  8. additiondiluted with EtOAc (300 mL)
  9. additionBrine (100 mL) is added
  10. customthe two layers are separated in a separatory funnel
  11. washThe organic layer is rinsed with water (2×75 mL)
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationThe organic layer is then concentrated
  14. custompurified

Sources & evidence

ORD record
ord-e29b9b927bbc4ed9bc4c92872c978d09
Source dataset
uspto-grants-2009_05
Patent number
US07528160B2

Reaction notes

Loading…