Water → (5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(pyridin-4-yl)ethenyl]pyrrolidin-2-one

HRID 70632Notes

Reaction equation

HRID 70632 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([Sn](CCCC)(CCCC)CCCC)=[CH:3][CH:2]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.Br/[C:37](/[C:45]1[CH:50]=[CH:49][C:48]([CH:51]2[CH2:53][CH2:52]2)=[C:47]([O:54][CH3:55])[N:46]=1)=[CH:38]\[C@@H:39]1[NH:43][C:42](=[O:44])[CH2:41][CH2:40]1.O>O1CCOCC1.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]>[CH:51]1([C:48]2[CH:49]=[CH:50][C:45](/[C:37](/[C:4]3[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=3)=[CH:38]/[C@@H:39]3[NH:43][C:42](=[O:44])[CH2:41][CH2:40]3)=[N:46][C:47]=2[O:54][CH3:55])[CH2:52][CH2:53]1

Participants

7

Reactant 4

HCID 962WaterHCID 521585Tris(furan-2-yl)phosphaneHCID 27373184-(Tri-n-butylstannyl)pyridineHCID 58452792(5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Product 1

HCID 67398901(5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(pyridin-4-yl)ethenyl]pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Pyridyltributyltin (218 mg), tris(dibenzylideneacetone)dipalladium (27 mg) and tri(2-furyl)phosphine (42 mg) were added to a solution of (5R)-5-[(Z)-2-bromo-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one obtained in Reference Example 4-24 (100 mg) in 1,4-dioxane (2 mL), and the mixture was stirred at 90° C. for four hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by NH-silica gel column chromatography (hexane:ethyl acetate=1:1→0:1) to give (5R)-5-[(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(pyridin-4-yl)ethenyl]pyrrolidin-2-one as a colorless amorphous (42 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe residue was purified by NH-silica gel column chromatography (hexane:ethyl acetate=1:1→0:1)

Sources & evidence

ORD record
ord-ba9cd757a59246dd892d1e89dfc17ab1
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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