Isopropanol → 1,2,3,3 a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, isopropyl ester

HRID 258144Notes

Reaction equation

HRID 258144 reaction equation
[O:1]=[C:2]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[CH:12]1[N:18]([CH3:21])[CH2:19][CH2:20][C:11]21[CH3:22])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH:23](O)(C)C>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[O:1]=[C:2]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[CH:12]1[N:18]([CH3:21])[CH2:19][CH2:20][C:11]21[CH3:22])[C:3]([O:5][CH:6]([CH3:23])[CH3:7])=[O:4]

Participants

4

Reactant 2

HCID 3776IsopropanolHCID 867464181,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, ethyl ester

Product 1

HCID 867464201,2,3,3 a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, isopropyl ester

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Conditions

Temperature
0 °C

Procedure

To a chilled (0° C.), stirred solution of 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, ethyl ester (0.68 g) in anhydrous isopropyl alcohol (10.2 ml) was added titanium (IV) ethoxide (0.17 ml) via syringe under a nitrogen atmosphere. The solution was warmed to room temperature and refluxed for 6.5 hours. The isopropyl alcohol was removed under reduced pressure and the residue dissolved in ethyl acetate (100 ml). The solution was washed twice with 50 ml portions of saturated aqueous NH4Cl solution, twice with 50 ml portions of saturated aqueous NaHCO3 solution and once with 50 ml of brine. The organic and aqueous phases were separated and the organic phase dried (Na2SO4), filtered, and concentrated to an oil. The crude mixture was purified using preparative HPLC (silica gel, 35% ethyl acetate in dichloromethane as the loading solvent and eluent). The appropriate fractions were combined and the solvents were removed under reduced pressure yielding 0.54 g of 1,2,3,3 a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, isopropyl ester, as an oil.

Workup

  1. temperatureThe solution was warmed to room temperature
  2. temperaturerefluxed for 6.5 hours
  3. customThe isopropyl alcohol was removed under reduced pressure
  4. dissolutionthe residue dissolved in ethyl acetate (100 ml)
  5. washThe solution was washed twice with 50 ml portions of saturated aqueous NH4Cl solution, twice with 50 ml portions of saturated aqueous NaHCO3 solution and once with 50 ml of brine
  6. customThe organic and aqueous phases were separated
  7. dry with materialthe organic phase dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe crude mixture was purified
  11. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-28784d0a745f4b09a040c9b1abab93bd
Source dataset
uspto-grants-1993_11
Patent number
US05264587

Reaction notes

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