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Ethyl bromoacetate → Ethyl(3-ethyl-1-(4-methoxybenzyl)-2-oxopyrrolidin-3-yl)acetate

HRID 714800
Notes
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Reaction equation

HRID 714800 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([CH:15]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:16]1=[O:29])[CH3:14].Br[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].[Cl-].[NH4+]>O1CCCC1>[CH2:35]([O:34][C:32](=[O:33])[CH2:31][C:15]1([CH2:13][CH3:14])[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:16]1=[O:29])[CH3:36]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 7748Ethyl bromoacetateHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 1178407281-(4-Methoxybenzyl)-3-ethylpyrrolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 131734071Ethyl(3-ethyl-1-(4-methoxybenzyl)-2-oxopyrrolidin-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (3.4 mL) in tetrahydrofuran (10 mL) was added dropwise n-butyllithium (1.6 M hexane solution, 15 mL) at −78° C. under nitrogen atmosphere, and the mixture was warmed to 0° C., and stirred for 30 min. The reaction mixture was cooled to −78° C., a solution of 3-ethyl-1-(4-methoxybenzyl)pyrrolidin-2-one (2.8 g) obtained in Step B in tetrahydrofuran (10 mL) was added thereto, and the mixture was stirred at the same temperature for 1 hr. Ethyl bromoacetate (4.0 mL) was added thereto, and the mixture was stirred overnight while it was allowed to be warmed. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.5 g).

Workup

  1. temperatureThe reaction mixture was cooled to −78° C.
  2. stirringthe mixture was stirred at the same temperature for 1 hr
  3. stirringthe mixture was stirred overnight while it
  4. temperatureto be warmed
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe obtained organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-06bcd36995a545efaef946f59634834a
Source dataset
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09187453B2

Reaction notes

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