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Benzyl Bromide → Dimethyl 4-benzyl-2-oxoglutarate dimethyl acetal

HRID 2352287
Notes
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Reaction equation

HRID 2352287 reaction equation
C(NC(C)C)(C)C.[CH3:8][O:9][C:10]([O:21][CH3:22])([O:19][CH3:20])[C:11](=[O:18])[CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CN(C)P(N(C)C)(N(C)C)=O>O1CCCC1.[Cl-].[NH4+]>[CH3:22][O:21][C:10]([O:19][CH3:20])([O:9][CH3:8])[C:11](=[O:18])[CH2:12][CH:13]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:14]([O:16][CH3:17])=[O:15]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 7912DiisopropylamineHCID 12679HexamethylphosphoramideHCID 54075676Dimethyl 2-oxoglutarate dimethyl acetal

Product 1

HCID 54120089Dimethyl 4-benzyl-2-oxoglutarate dimethyl acetal

Reagents, catalysts & solvents 2

HCID 8028
Tetrahydrofuran
Solvent
3×
HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 0.98 ml diisopropylamine in 13 ml anhydrous tetrahydrofuran 4.29 ml 1.5M n-butyllithium (in hexane solution) was added under nitrogen gas atmosphere, while stirring the solution at -78° C. After the mixture was stirred for 15 minutes, a solution of 1.18 g dimethyl 2-oxoglutarate dimethyl ketal in 7 ml anhydrous tetrahydrofuran was added over a period of 15 minutes, then the resulting mixture was stirred for 15 minutes. A solution of 0.76 ml benzyl bromide and 0.28 ml hexamethylphosphoramide in 7 ml anhydrous tetrahydrofuran was added over a period of 5 minutes, and the resulting mixture was stirred at -78° C. for 30 minutes. The reaction mixture, after raising temperature to -20° C. over a period of 2 hours with stirring, was diluted with a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The resulting extract was washed with water and dried (MgSO4), then the solvent was evaporated. The resulting residue was eluted with hexane-ethyl acetate (5:1→2:1) via column chromatography using silica gel to yield 1.64 g dimethyl 4-benzyl-2-oxoglutarate dimethyl ketal in the form of a light yellow oily substance.

Workup

  1. stirringAfter the mixture was stirred for 15 minutes
  2. stirringthe resulting mixture was stirred for 15 minutes
  3. stirringthe resulting mixture was stirred at -78° C. for 30 minutes
  4. temperatureThe reaction mixture, after raising temperature to -20° C. over a period of 2 hours
  5. stirringwith stirring
  6. extractionextracted with ethyl acetate
  7. extractionThe resulting extract
  8. washwas washed with water
  9. dry with materialdried (MgSO4)
  10. customthe solvent was evaporated
  11. washThe resulting residue was eluted with hexane-ethyl acetate (5:1→2:1) via column chromatography

Sources & evidence

ORD record
ord-b7180e28b7f54e43a16cd85ab27f1729
Source dataset
uspto-grants-1989_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04876251

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes