Cesium carbonate → 2-chloro-4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-3-fluorobenzonitrile

HRID 1173734ノート

反応式

HRID 1173734 の反応式
[Si]([O:8][C@@H:9]1[C@H:13]([CH2:14][CH3:15])[NH:12][C:11](=[O:16])[CH2:10]1)(C(C)(C)C)(C)C.[Cl:17][C:18]1[C:25]([F:26])=[C:24](I)[CH:23]=[CH:22][C:19]=1[C:20]#[N:21].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:17][C:18]1[C:25]([F:26])=[C:24]([N:12]2[C:11](=[O:16])[CH2:10][C@H:9]([OH:8])[C@@H:13]2[CH2:14][CH3:15])[CH:23]=[CH:22][C:19]=1[C:20]#[N:21]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595568762-Chloro-3-fluoro-4-iodobenzonitrileHCID 67105254(4S,5S)-4-(tert-butyldimethylsilyloxy)-5-ethylpyrrolidin-2-one

生成物 1

HCID 595568712-chloro-4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-3-fluorobenzonitrile収率 25%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of (4S,5S)-4-(tert-butyldimethylsilyloxy)-5-ethylpyrrolidin-2-one (300 mg), 2-chloro-3-fluoro-4-iodobenzonitrile (416 mg), cesium carbonate (602 mg), tris(dibenzylideneacetone)dipalladium(0) (56.4 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (107 mg) in dioxane (10 mL) was stirred at 80° C. overnight under an argon atmosphere. After allowing to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane→hexane-ethyl acetate=2:1). The obtained residue was dissolved in ethanol (10 mL)-tetrahydrofuran (10 mL), concentrated hydrochloric acid (2.06 mL) was added, and the mixture was stirred overnight at room temperature. The mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution under ice-cooling, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane→ethyl acetate), and recrystallized from hexane-ethyl acetate to give the title compound as colorless crystals (yield: 86 mg, 25%).

後処理

  1. customAfter allowing to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (eluent: hexane→hexane-ethyl acetate=2:1)
  7. dissolutionThe obtained residue was dissolved in ethanol (10 mL)-tetrahydrofuran (10 mL), concentrated hydrochloric acid (2.06 mL)
  8. additionwas added
  9. temperaturecooling
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over magnesium sulfate
  13. customthe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane→ethyl acetate)
  15. customrecrystallized from hexane-ethyl acetate

出典と根拠

ORDレコード
ord-9a16ed46c09748a18c07641a4c814d27
出典データセット
uspto-grants-2010_11
特許番号
US07834051B2

反応ノート

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