Cesium carbonate → (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

HRID 70634

反応式

HRID 70634 の反応式
Br/[C:2](/[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH3:18])[N:11]=1)=[CH:3]\[C@@H:4]1[NH:8][C:7](=[O:9])[CH2:6][CH2:5]1.[C:19]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)([CH3:22])([CH3:21])[CH3:20].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>[C:19]([C:23]1[CH:28]=[CH:27][C:26](/[C:2](/[C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH3:18])[N:11]=2)=[CH:3]\[C@@H:4]2[NH:8][C:7](=[O:9])[CH2:6][CH2:5]2)=[CH:25][CH:24]=1)([CH3:22])([CH3:21])[CH3:20]

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 27343204-tert-Butylphenylboronic acidHCID 58452317(5R)-5-[(Z)-2-bromo-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

生成物 1

HCID 67399368(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(5-chloro-6-methoxypyridin-2-yl)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 (8 mL) and water (2 mL) were added to a mixture of (5R)-5-[(Z)-2-bromo-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one obtained in Reference Example 4-18 (531 mg), 4-tert-butylphenylboronic acid (570 mg), tris(dibenzylideneacetone)dipalladium (147 mg), tri(2-furyl)phosphine (224 mg) and cesium carbonate (1.04 g), and the mixture was stirred at 90° C. for 2.5 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=90:10→60:40) to give (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one as a pale yellow amorphous (597 mg).

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=90:10→60:40)

出典と根拠

ORDレコード
ord-0a07b60038914258a447b1f7561a0e9c
出典データセット
uspto-grants-2014_09
特許番号
US08822503B2

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