Ethyl bromoacetate → ethyl [1-hexyl-3-(6-hydroxy-1,3-benzodioxol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]acetate

HRID 1259624Notes

Reaction equation

HRID 1259624 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]([C:28]2[C:36]([OH:37])=[CH:35][C:31]3[O:32][CH2:33][O:34][C:30]=3[CH:29]=2)[C:20]1=[O:38])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].Br[CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>C1COCC1>[CH2:13]([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])([C:28]2[C:36]([OH:37])=[CH:35][C:31]3[O:32][CH2:33][O:34][C:30]=3[CH:29]=2)[C:20]1=[O:38])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 7912DiisopropylamineHCID 588725471-hexyl-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-oneHCID 178418339Butyllithium

Product 1

HCID 58872453ethyl [1-hexyl-3-(6-hydroxy-1,3-benzodioxol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]acetateYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

To a solution of diisopropylamine (1.14 g, 11.0 mmol) in THF (10.0 mL) was added n-butyl lithium (7.00 mL, 11.0 mmol, 1.6 M solution in hexane) at −75° C. The resulting mixture was stirred at −75° C. for half an hour and added slowly to a solution of 1-hexyl-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one in THF (20.0 mL) at −75° C. After stirring at −75° C. for another half an hour, ethyl bromoacetate was added. The mixture was stirred at ambient temperature for 18 hrs and quenched with saturated ammonium chloride solution. The organic solvent was removed in vacuo and the aqueous residue was diluted with ethyl acetate (100 mL). The organic layer was washed with saturated ammonium chloride (25.0 mL), brine (50.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography eluting with 40% EtOAc/Hexanes to yield the title compound (0.19 g, 8%) as an oil: MS (ES+) m/z 440.5 (M+1).

Workup

  1. stirringAfter stirring at −75° C. for another half an hour
  2. stirringThe mixture was stirred at ambient temperature for 18 hrs
  3. customquenched with saturated ammonium chloride solution
  4. customThe organic solvent was removed in vacuo
  5. additionthe aqueous residue was diluted with ethyl acetate (100 mL)
  6. washThe organic layer was washed with saturated ammonium chloride (25.0 mL), brine (50.0 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo to dryness
  10. washeluting with 40% EtOAc/Hexanes

Sources & evidence

ORD record
ord-da367db3a1664c4d98160e3fa564352c
Source dataset
uspto-grants-2013_06
Patent number
US08466188B2

Reaction notes

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