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

HRID 70658Notes

Reaction equation

HRID 70658 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:33]1[CH:34]=[CH:35][C:36](/[C:41](/[C:49]2[CH:54]=[CH:53][C:52]([C:55]([CH3:58])([CH3:57])[CH3:56])=[CH:51][CH:50]=2)=[CH:42]/[C@@H:43]2[NH:47][C:46](=[O:48])[CH2:45][CH2:44]2)=[N:37][C:38]=1[O:39][CH3:40]>O1CCOCC1.C(OCC)(=O)C.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].O>[C:55]([C:52]1[CH:53]=[CH:54][C:49](/[C:41](/[C:36]2[CH:35]=[CH:34][C:33]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:38]([O:39][CH3:40])[N:37]=2)=[CH:42]\[C@@H:43]2[NH:47][C:46](=[O:48])[CH2:45][CH2:44]2)=[CH:50][CH:51]=1)([CH3:58])([CH3:57])[CH3:56]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 521585Tris(furan-2-yl)phosphaneHCID 58452636(5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]pyrrolidin-2-one

Product 1

HCID 67397019(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(6-methoxy-5-phenylpyridin-2-yl)ethenyl]pyrrolidin-2-one

Reagents, catalysts & solvents 4

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

Conditions

Temperature
65 °C

Procedure

Phenylboronic acid (57 mg), tris(dibenzylideneacetone)dipalladium(0) (19 mg), tri(2-furyl)phosphine (32 mg) and cesium carbonate (151 mg) were added to a solution of (5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]pyrrolidin-2-one obtained in Reference Example 4-42 (80 mg) in 1,4-dioxane (1.5 mL)-water (0.5 mL), and the mixture was stirred at an external temperature of 65° C. for three hours. The reaction solution was left to cool, diluted with ethyl acetate and filtered. The filtrate was washed with brine and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:2) to give (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(6-methoxy-5-phenylpyridin-2-yl)ethenyl]pyrrolidin-2-one as an orange oil (81 mg).

Workup

  1. waitThe reaction solution was left
  2. temperatureto cool
  3. filtrationfiltered
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:2)

Sources & evidence

ORD record
ord-e796418d2b9f433caca48e576b24ad79
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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