Cesium carbonate → 4-methoxy-5-styryl-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

HRID 475093ノート

反応式

HRID 475093 の反応式
Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[CH:7]=[N:8][C:4]=2[C:3]=1[O:17][CH3:18].[CH:19](/B(O)O)=[CH:20]\[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[CH3:18][O:17][C:3]1[C:4]2[N:8]=[CH:7][N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[C:5]=2[CH:15]=[CH:16][C:2]=1[CH:19]=[CH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 5702628Styrylboronic acidHCID 712726975-bromo-4-methoxy-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

生成物 1

HCID 866946894-methoxy-5-styryl-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole収率 77.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A 1 L three-necked round bottom flask fitted with an overhead stirrer was dried and cooled under a stream of nitrogen then charged with 5-bromo-4-methoxy-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (30 g, 0.096 mol, 1.0 equiv.) in 1,4-dioxane (300 mL) and water (60 mL). The mixture was degassed with nitrogen. To the degassed solution at RT was added sequentially trans-β-styrene boronic acid (14.26 g, 0.096 mol, 1.0 equiv.), Cs2CO3 (62.82 g, 0.19 mol, 2.0 equiv.), Pd(II)Cl2(PPh3)2 (3.38 g, 0.004 mol, 0.05 equiv.) then the reaction was heated with stirring at 100° C. for 6 h. The reaction mixture was quenched with ice cold water (1 L) and extracted with EtOAc (2×1 L). The organic layers were combined, washed with brine solution (500 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (40-50% EtOAc) to afford 4-methoxy-5-styryl-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (25 g, 77%) as a brown solid.

後処理

  1. customA 1 L three-necked round bottom flask fitted with an overhead stirrer
  2. customwas dried
  3. temperaturecooled under a stream of nitrogen
  4. customThe mixture was degassed with nitrogen
  5. temperaturethe reaction was heated
  6. customThe reaction mixture was quenched with ice cold water (1 L)
  7. extractionextracted with EtOAc (2×1 L)
  8. washwashed with brine solution (500 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by SiO2 chromatography
  13. washeluting with an EtOAc/hexane gradient (40-50% EtOAc)

出典と根拠

ORDレコード
ord-464c9952a5d74160a8dbaf377348bc54
出典データセット
uspto-grants-2014_01
特許番号
US08637537B2

反応ノート

読み込み中…