Citric Acid → 1,1-Dimethylethyl (3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]-3-pyrrolidinecarboxylate

HRID 17629Notes

Reaction equation

HRID 17629 reaction equation
CI.[O:3]=[C:4]1[N:8]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH2:7][CH:6]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:5]1.[H-].[Na+].[C:26](O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[CH3:26][C@:6]1([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:5][C:4](=[O:3])[N:8]([C@@H:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH3:10])[CH2:7]1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 57758674HCID 57758674, compound

Product 1

HCID 577587301,1-Dimethylethyl (3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]-3-pyrrolidinecarboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl iodide (21.8 ml, 0.35 mol) was added to an N,N-dimethylformamide (150 ml) solution of tert-butyl 5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (I-341) (20.28 g, 70.1 mmol), then at room temperature, sodium hydride (55%, w/w) (1 g) was added, followed by stirring as such. Afterwards, sodium hydride (1.9 g, 2.7 g, 2.79 g, 1.97 g) was successively added, followed by stirring at room temperature for 13 hours. With cooling with ice, aqueous 10% citric acid solution was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated away. The resulting residue was separated and purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=3:1, v/v) to obtain the entitled compound (7.65 g, 36%).

Workup

  1. stirringby stirring at room temperature for 13 hours
  2. additionwas added to the reaction liquid
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated away
  7. customThe resulting residue was separated
  8. custompurified by silica gel column chromatography (eluent, n-hexane

Sources & evidence

ORD record
ord-b8b8593e8b2043cab1ab7f4ff246ae1c
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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