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

HRID 408024ノート

反応式

HRID 408024 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0fa575c4b3cc42ea9c6dbbaae148a9be
出典データセット
uspto-grants-2014_06
特許番号
US08754226B2

反応ノート

読み込み中…