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

HRID 70634

Reaction equation

HRID 70634 reaction equation
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]

Participants

9

Reactant 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

Product 1

HCID 67399368(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-0a07b60038914258a447b1f7561a0e9c
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

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