Potassium Acetate → 1-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile

HRID 1028007ノート

反応式

HRID 1028007 の反応式
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]#[N:16])=[CH:7][N:8]2[CH:11]2[CH2:14][CH2:13][CH2:12]2)=[CH:4][C:3]=1[F:17].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:19]1.C([O-])(=O)C.[K+].OOS([O-])=O.[K+]>O1CCOCC1.O.C(OCC)(=O)C>[CH:11]1([N:8]2[C:9]3[C:5](=[CH:4][C:3]([F:17])=[C:2]([OH:19])[CH:10]=3)[C:6]([C:15]#[N:16])=[CH:7]2)[CH2:14][CH2:13][CH2:12]1

参加物

8

反応物 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 23707502Potassium hydroxy sulfiteHCID 667306106-bromo-1-cyclobutyl-5-fluoro-1H-indole-3-carbonitrile

生成物 1

HCID 681080201-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile収率 82%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A mixture of 6-bromo-1-cyclobutyl-5-fluoro-1H-indole-3-carbonitrile (29.9 g, 102 mmol), bis(pinacolato)diboron (33.7 g, 133 mmol), PdCl2dppf-CH2Cl2 complex (4.16 g, 5.1 mmol) and potassium acetate (30 g, 306 mmol) in dioxane (300 mL) was stirred at 80° C. overnight. The mixture was then cooled to room temperature, treated with ethyl acetate (200 mL) and filtered through a silica-celite pad. The filtrate was concentrated, dissolved in acetone (300 mL) and cooled to 0° C. Into this solution was added a slurry of Oxone (125.5 g, 204 mmol) in water (300 mL). The mixture was stirred at room temperature for 15 min, diluted with ethyl acetate and separated. The aqueous layer was extracted with ethyl acetate. The organic extractions were combined and washed with sat. aq. NaHSO3, and brine, dried over Na2SO4 and concentrated. The residue was purified on silica gel to provide 1-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile as a light grey solid (19.2 g, 82%).

後処理

  1. temperatureThe mixture was then cooled to room temperature
  2. filtrationfiltered through a silica-celite pad
  3. concentrationThe filtrate was concentrated
  4. dissolutiondissolved in acetone (300 mL)
  5. temperaturecooled to 0° C
  6. stirringThe mixture was stirred at room temperature for 15 min
  7. customseparated
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. extractionThe organic extractions
  10. washwashed with sat. aq. NaHSO3, and brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customThe residue was purified on silica gel

出典と根拠

ORDレコード
ord-9d0c8ffecc2b46f9b63403ee9c36d05b
出典データセット
uspto-grants-2014_05
特許番号
US08735414B2

反応ノート

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