N,N,N',N'-Tetramethylethylenediamine → 1,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diisopropyl amide

HRID 1681638Notes

Reaction equation

HRID 1681638 reaction equation
CN(CCN(C)C)C.C([Li])(CC)C.Br[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH3:24])[CH:19]1[N:25]([CH3:28])[CH2:26][CH2:27][C:18]21[CH3:29].[CH:30]([N:33]([C:37](=[O:43])[C:38](OCC)=[O:39])[CH:34]([CH3:36])[CH3:35])([CH3:32])[CH3:31]>CCOCC>[CH:34]([N:33]([CH:30]([CH3:32])[CH3:31])[C:37](=[O:43])[C:38](=[O:39])[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH3:24])[CH:19]1[N:25]([CH3:28])[CH2:26][CH2:27][C:18]21[CH3:29])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 11816503Ethyl [di(propan-2-yl)amino](oxo)acetateHCID 197825615-Bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indoleHCID 178418400CID 53628100

Product 1

HCID 867464211,2,3,3a,8,8a-Hexahydro-alpha-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diisopropyl amideYield 58%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of TMEDA (2.85 ml) in anhydrous ether (5.0 ml) was added at -78° C. under N2 atmosphere, sec-butyllithium (14.5 ml). The resulting solution was subsequently treated with a solution of 5-bromo-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indole (3.80 g) in anhydrous ether (10 ml). The mixture was held at this temperature for 3 hours and then added to a solution of diisopropylamino-oxo-acetic acid, ethyl ester (7.5 g) in anhydrous ether (15 ml). After stirring at -78° C. for 4 hours, the reaction mixture was quenched with 50 ml of aqueous NH4Cl solution. The organic and aqueous phases were separated and the organic phase washed successively with saturated aqueous NaHCO3 and brine. The organic phase was dried (Na2SO4), filtered and concentrated to an oil which was purified by HPLC (silica gel, 10% MeOH in ethyl acetate as eluent). 2.8 g of 1,2,3,3a,8,8a-Hexahydro-α-oxo- 1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, diisopropyl amide was obtained as a foam. Trituration with hexane and drying under reduced pressure yielded an analytically pure sample.

Workup

  1. customthe reaction mixture was quenched with 50 ml of aqueous NH4Cl solution
  2. customThe organic and aqueous phases were separated
  3. washthe organic phase washed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to an oil which
  7. customwas purified by HPLC (silica gel, 10% MeOH in ethyl acetate as eluent)

Sources & evidence

ORD record
ord-7ec26e5452d4443c9f519a1e6ef6290a
Source dataset
uspto-grants-1992_12
Patent number
US05173497

Reaction notes

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