Methyl iodide → (S)-1-(2,6-dimethylphenyl)-3-isobutyl-4-methyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

HRID 2068253노트

반응식

HRID 2068253 반응식
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13]([C@@:15]1([CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:19][C:18](=[O:20])[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[CH2:16]1)=[O:14].I[CH3:34].[NH4+].[Cl-]>C1COCC1>[CH3:11][O:12][C:13]([C@@:15]1([CH2:29][CH:30]([CH3:32])[CH3:31])[CH:19]([CH3:34])[C:18](=[O:20])[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:28])[CH2:16]1)=[O:14]

참가 물질

6

반응물 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 58218845(S)-1-(2,6-dimethyl-phenyl)-3-isobutyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

생성물 1

HCID 58218854(S)-1-(2,6-dimethylphenyl)-3-isobutyl-4-methyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester수율 28%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

LHMDS (1 M solution in THF, 1.78 mL, 1.78 mmol) was added slowly to a cooled (−50° C.) solution of (S)-1-(2,6-dimethylphenyl)-3-isobutyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared from step e, 450 mg, 1.48 mmol) in THF (10 mL). After 5 min, iodomethane (185 μL, 2.97 mmol) was added at −50° C. and the resulting reaction mixture was immediately warmed to room temperature and stirred further for 2 h. Saturated aqueous NH4Cl solution (25 mL) was added, and the solution was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 20→60% MTBE/hexanes) to give (S)-1-(2,6-dimethylphenyl)-3-isobutyl-4-methyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (130 mg, 28% yield). LC-MS: Rt (retention time): 2.68 min, MS: (ES) m/z 318.2 (M+H+).

후처리

  1. customthe resulting reaction mixture
  2. extractionthe solution was extracted with EtOAc (3×50 mL)
  3. washThe combined organic layers were washed with water (50 mL), brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by flash chromatography (SiO2, 20→60% MTBE/hexanes)

출처 및 근거

ORD 기록
ord-1f70ad8fc7764d73ae4945ff93b96a41
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293925B2

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