Sodium Carbonate → tert-butyl 4-((S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate

HRID 408024노트

반응식

HRID 408024 반응식
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C:8]2([CH3:21])[CH3:20])[C:3]1=[O:22].F[C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=1[F:34].C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O>[F:34][C:25]1[CH:26]=[C:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=[CH:29][C:24]=1[NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:9][C:8]2([CH3:21])[CH3:20])[C:3]1=[O:22]

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 27827431,2-Difluoro-4-(methylsulfonyl)benzeneHCID 67469742tert-butyl 4-((S)-3-amino-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate

생성물 1

HCID 67469764tert-butyl 4-((S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate수율 16.2%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
120 °C

실험 절차

tert-Butyl 4-((S)-3-amino-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate (0.40 g, 1.3 mmol) was dissolved in DMSO (5 mL). 1,2-Difluoro-4-(methylsulfonyl)benzene (0.32 g, 1.7 mmol) and powdered Na2CO3 (0.18 g, 1.7 mmol) were added. The reaction mixture was bubbled under nitrogen for 15 minutes. The mixture stirred overnight at 120° C. The reaction mixture was cooled to ambient temperature and partitioned between brine and ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and concentrated. Flash chromatography of the crude material on silica gel followed by reverse phase HPLC purification gave tert-butyl 4-((S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate (0.10 g, 0.21 mmol, 16% yield) as a white solid.

후처리

  1. customThe reaction mixture was bubbled under nitrogen for 15 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. custompartitioned between brine and ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customFlash chromatography of the crude material on silica gel followed by reverse phase HPLC purification

출처 및 근거

ORD 기록
ord-0fa575c4b3cc42ea9c6dbbaae148a9be
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754226B2

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