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

HRID 258143Notes

Reaction equation

HRID 258143 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].[NH4+].[Cl-].C(Cl)Cl>C1(CCO)C=CC=CC=1.[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][CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:14]=[CH:15][CH:16]=1)=[O:4]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 25517Ammonium ChlorideHCID 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 867464191,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, phenylethyl esterYield 151.4%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 60542-PhenylethanolSolvent

Procedure

To a chilled (0° C.) 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 (0.76 g) in anhydrous phenylethyl alcohol (18.1 ml) was added titanium (IV) ethoxide (0.22 ml) via syringe under a nitrogen atmosphere. The solution was warmed to room temperature and heated to just under reflux for 3 hours. The solution was then cooled to 0° C. and saturated NH4Cl solution was added slowly until a precipitate formed. Methylene chloride (200 ml) was then added and the mixture extracted twice with 100 ml portions of saturated aqueous NH4Cl solution, twice with 100 ml of saturated aqueous NaHCO3 and once with 100 ml of brine. The organic extracts were dried (Na2SO4), filtered, and the solvent removed on the rotary evaporator. The phenylethyl alcohol was then removed by distillation under high vacuum. The resulting residue was purified using preparative HPLC (silica gel, 4% methanol in ethyl acetate as the loading solvent and eluent). The appropriate fractions were combined, and the solvent removed to yield 0.72 g of 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, phenylethyl ester, as an oil.

Workup

  1. temperatureheated to just
  2. temperatureunder reflux for 3 hours
  3. temperatureThe solution was then cooled to 0° C.
  4. customformed
  5. extractionthe mixture extracted twice with 100 ml portions of saturated aqueous NH4Cl solution, twice with 100 ml of saturated aqueous NaHCO3 and once with 100 ml of brine
  6. dry with materialThe organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent removed on the rotary evaporator
  9. customThe phenylethyl alcohol was then removed by distillation under high vacuum
  10. customThe resulting residue was purified
  11. customthe solvent removed

Sources & evidence

ORD record
ord-788199bd2a504ac29c913a4d5d4ff9b3
Source dataset
uspto-grants-1993_11
Patent number
US05264587

Reaction notes

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