Potassium Fluoride → 3-(8-Benzyl-8-azabicyclo[3.2.1]oct-2-en-3-yl)benzamide

HRID 549811ノート

反応式

HRID 549811 の反応式
[C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=1)(=[O:3])[NH2:2].[F-].[K+].[CH2:15]([N:22]1[CH:27]2[CH2:28][CH2:29][CH:23]1[CH:24]=[C:25](OS(C(F)(F)F)(=O)=O)[CH2:26]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1COCC1>[CH2:15]([N:22]1[CH:27]2[CH2:28][CH2:29][CH:23]1[CH:24]=[C:25]([C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:1]([NH2:2])=[O:3])[CH2:26]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

参加物

7

反応物 3

HCID 522689Potassium FluorideHCID 2737814(3-Carbamoylphenyl)boronic acidHCID 498359108-Benzyl-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-ene

生成物 1

HCID 671012843-(8-Benzyl-8-azabicyclo[3.2.1]oct-2-en-3-yl)benzamide

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
67 °C

実験手順

To the crude product of the previous step was added THF (420 mL) and the solution was purged with nitrogen for 5 min. To a 2 L flask was added 3-carbamoylphenyl boronic acid (98%, 33.0 g, 200 mmol), palladium (II) acetate (98%. 0.46 g, 2 mmol), 1,1′-bis(diphenylphosphino)ferrocene (97%, 1.1 g, 2 mmol). and potassium fluoride (34.9 g, 600 mmol) followed by the THF solution of trifluoro-methanesulfonic acid 8-benzyl-8-aza-bicyclo[3.2.1]oct-2-en-3-yl ester. The resulting mixture was purged with nitrogen for 5 min, heated to reflux (67° C.) under nitrogen and stirred for 2 h. The reaction mixture was cooled to 30° C., then EtOAc (500 mL) and 1 N NaOH (500 mL) were added and the mixture was stirred at 22° C. for 10 min. The layers were separated and the aqueous layer was discarded. The organic layer was washed with a mixture of brine (250 mL) and water (250 mL) and stirred for 5 min. The layers were separated and the aqueous layer was discarded. The organic layer was briefly dried over Na2SO4, filtered, and solvent was partially removed. Product precipitated as light yellow solids during solvent removal. The resulting slurry (about 200 mL) was filtered and the solids were washed with cold EtOAc (0° C., 100 mL) and dried under high vacuum at 25° C. to provide the title intermediate (42.5 g) as a light yellow solid.

後処理

  1. customthe solution was purged with nitrogen for 5 min
  2. customThe resulting mixture was purged with nitrogen for 5 min
  3. temperatureheated
  4. temperatureThe reaction mixture was cooled to 30° C.
  5. additionEtOAc (500 mL) and 1 N NaOH (500 mL) were added
  6. stirringthe mixture was stirred at 22° C. for 10 min
  7. customThe layers were separated
  8. washThe organic layer was washed with a mixture of brine (250 mL) and water (250 mL)
  9. stirringstirred for 5 min
  10. customThe layers were separated
  11. dry with materialThe organic layer was briefly dried over Na2SO4
  12. filtrationfiltered
  13. customsolvent was partially removed
  14. customProduct precipitated as light yellow solids during solvent removal
  15. filtrationThe resulting slurry (about 200 mL) was filtered
  16. washthe solids were washed with cold EtOAc (0° C., 100 mL)
  17. customdried under high vacuum at 25° C.

出典と根拠

ORDレコード
ord-1cef673e494b43e5b1d7e95e70426867
出典データセット
uspto-grants-2011_05
特許番号
US07943772B2

反応ノート

読み込み中…