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

HRID 2068245노트

반응식

HRID 2068245 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-ab4ac8913a294567940806d0fe7d7da6
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293925B2

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