Cesium carbonate → (5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethenyl]pyrrolidin-2-one

HRID 70679ノート

反応式

HRID 70679 の反応式
Br/[C:2](/[C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:18][CH2:17]2)=[C:12]([O:19][CH3:20])[N:11]=1)=[CH:3]\[C@@H:4]1[NH:8][C:7](=[O:9])[CH2:6][CH2:5]1.[Cl:21][C:22]1[CH:23]=[C:24](OB(O)O)[CH:25]=[CH:26][C:27]=1[Cl:28].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C(OCC)(=O)C.O.O1CCOCC1>[CH:16]1([C:13]2[CH:14]=[CH:15][C:10](/[C:2](/[C:25]3[CH:24]=[CH:23][C:22]([Cl:21])=[C:27]([Cl:28])[CH:26]=3)=[CH:3]/[C@@H:4]3[NH:8][C:7](=[O:9])[CH2:6][CH2:5]3)=[N:11][C:12]=2[O:19][CH3:20])[CH2:18][CH2:17]1

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 219399273,4-Dichloro-phenyl-boric acidHCID 58452792(5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

生成物 1

HCID 67397284(5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethenyl]pyrrolidin-2-one

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

1,4-Dioxane (4 mL) and water (0.5 mL) were added to a mixture of (5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one (300 mg), 3,4-dichlorophenylboric acid (340 mg), tris(dibenzylideneacetone)dipalladium (81 mg), tri(2-furyl) phosphine (124 mg) and cesium carbonate (867 mg), and the mixture was stirred at 90° C. for three hours. Water and ethyl acetate were added to the reaction solution and the insoluble matter was filtered off through celite, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50→0:100) to give (5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethenyl]pyrrolidin-2-one as a colorless amorphous (250 mg, 69%).

後処理

  1. filtrationthe insoluble matter was filtered off through celite
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50→0:100)

出典と根拠

ORDレコード
ord-46abfe357f1a462e887b20e9281d55dc
出典データセット
uspto-grants-2014_09
特許番号
US08822503B2

反応ノート

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