Methyl iodide → 1-(2,6-Dimethylphenyl)-3-ethyl-4-methoxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

HRID 1020980Notes

Reaction equation

HRID 1020980 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1([CH2:22][CH3:23])[CH:11]([OH:12])[C:10](=[O:13])[N:9]([C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:21])[CH2:8]1)=[O:6].[CH3:24]I.[NH4+].[Cl-]>C1COCC1>[CH3:3][O:4][C:5]([C:7]1([CH2:22][CH3:23])[CH:11]([O:12][CH3:24])[C:10](=[O:13])[N:9]([C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:21])[CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 582188351-(2,6-Dimethyl-phenyl)-3-ethyl-4-hydroxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

Product 1

HCID 582187831-(2,6-Dimethylphenyl)-3-ethyl-4-methoxy-5-oxo-pyrrolidine-3-carboxylic acid methyl esterYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersed in mineral oil, 50 mg, ˜2.0 mmol) was added slowly to a cooled (0° C.) solution of 1-(2,6-dimethylphenyl)-3-ethyl-4-hydroxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared from step b, 146 mg, 0.5 mmol) in THF (5 mL). After stirring for 5 min, MeI (62.5 μL, 1 mmol) was added and the resulting reaction mixture was slowly warmed to room temperature and stirred further for 12 h. Saturated aqueous NH4Cl solution (10 mL) was added, and the solution was extracted with EtOAc (3×25 mL). The combined organic layer were washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 10→50% EtOAc/hexanes) to give 1-(2,6-dimethylphenyl)-3-ethyl-4-methoxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (70 mg, 46% yield). LC-MS: Rt (retention time): 2.31, 2.44 min (two diastereomers), MS: (ES) m/z 306.2 (M+H+).

Workup

  1. customthe resulting reaction mixture
  2. stirringstirred further for 12 h
  3. extractionthe solution was extracted with EtOAc (3×25 mL)
  4. washThe combined organic layer were washed with water (50 mL), brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe residue was purified by flash chromatography (SiO2, 10→50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9104d694a23d44e9bb8f47725ff789d9
Source dataset
uspto-grants-2014_05
Patent number
US08716494B2

Reaction notes

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