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

HRID 70629

반응식

HRID 70629 반응식
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:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(OCC)(=O)C.O.O1CCOCC1>[Cl:21][C:22]1[CH:27]=[CH:26][C:25](/[C:2](/[C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:18][CH2:17]3)=[C:12]([O:19][CH3:20])[N:11]=2)=[CH:3]\[C@@H:4]2[NH:8][C:7](=[O:9])[CH2:6][CH2:5]2)=[CH:24][CH:23]=1

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 742994-Chlorophenylboronic acidHCID 521585Tris(furan-2-yl)phosphaneHCID 58452792(5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

생성물 1

HCID 67399304(5R)-5-[(E)-2-(4-chlorophenyl)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

시약·촉매·용매 4

HCID 9832798Tris(dibenzylideneacetone) dipalladium촉매HCID 962Water용매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

1,4-Dioxane (4 mL) and water (0.4 mL) were added to a mixture of (5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one obtained in Reference Example 4-24 (170 mg), 4-chlorophenylboronic acid (160 mg), tris(dibenzylideneacetone) dipalladium (45 mg), tri(2-furyl)phosphine (69 mg) and cesium carbonate (492 mg), 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=50:50→0:100) to give (5R)-5-[(E)-2-(4-chlorophenyl)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one as a crude product (250 mg).

후처리

  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)

출처 및 근거

ORD 기록
ord-1ddef37346744936946e7026649bb908
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822503B2

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