Water → 5-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl-sulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-[2-(tert-butyldimethylsilyloxy)ethoxy]-benzene

HRID 1513002ノート

反応式

HRID 1513002 の反応式
[F:1][C:2]1[C:3]([N:23]2[C:31](=[O:32])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]2=[O:33])=[CH:4][C:5]([S:9]([N:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[CH2:16][CH2:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:41][CH2:42][O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45].O>CN(C)C=O>[F:1][C:2]1[C:3]([N:23]2[C:24](=[O:33])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]2=[O:32])=[CH:4][C:5]([S:9]([N:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[CH2:16][CH2:15][CH2:14][CH2:13]2)(=[O:10])=[O:11])=[C:6]([O:8][CH2:41][CH2:42][O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[CH:7]=1

参加物

6

反応物 4

HCID 962WaterHCID 10796Cesium carbonateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 593098855-Fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-ylsulfonyl)-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)phenol

生成物 1

HCID 685129195-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl-sulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-[2-(tert-butyldimethylsilyloxy)ethoxy]-benzene

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of 5-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl-sulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)phenol (0.46 g) and cesium carbonate (0.48 g) in N,N-dimethylformamide (5 mL) was added 1-bromo-2-(tert-butyl-dimethylsilyloxy)ethane (0.25 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane n-hexane/ethyl acetate=1/1) to give 5-fluoro-2-(2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl-sulfonyl)-4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-[2-(tert-butyldimethylsilyloxy)ethoxy]-benzene (66 mg). This material was dissolved in tetrahydrofuran (3 mL). To the solution was added hydrazine monohydrate (0.026 mL), and the mixture was heated at reflux for 2 hours. The reaction mixture was cooled to room temperature, and diluted with ethyl acetate. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=1/1) to give the title compound (52 mg).

後処理

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane n-hexane/ethyl acetate=1/1)

出典と根拠

ORDレコード
ord-cbdaabff60014bddb11ea408cd6b141c
出典データセット
uspto-grants-2012_07
特許番号
US08217069B2

反応ノート

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