Water → 3-Cyclopropyl-6-{(E)-1-[3-methoxy-4-(methylsulfonyl)phenyl]-2-[(2R)-5-oxopyrrolidin-2-yl]ethenyl}pyridin-2(1H)-one

HRID 70695Notes

Reaction equation

HRID 70695 reaction equation
[CH3:1][O-:2].[Na+].[CH:4]1([C:7]2[C:8](=[O:32])[NH:9][C:10](/[C:13](/[C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[C:23](F)[CH:22]=3)=[CH:14]/[C@H:15]3[CH2:19][CH2:18][C:17](=[O:20])[NH:16]3)=[CH:11][CH:12]=2)[CH2:6][CH2:5]1.O>CO>[CH:4]1([C:7]2[C:8](=[O:32])[NH:9][C:10](/[C:13](/[C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[C:23]([O:2][CH3:1])[CH:22]=3)=[CH:14]/[C@H:15]3[CH2:19][CH2:18][C:17](=[O:20])[NH:16]3)=[CH:11][CH:12]=2)[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 962WaterHCID 10942334Sodium Methoxide3×HCID 58452593HCID 58452593, compound2×

Product 1

HCID 584523713-Cyclopropyl-6-{(E)-1-[3-methoxy-4-(methylsulfonyl)phenyl]-2-[(2R)-5-oxopyrrolidin-2-yl]ethenyl}pyridin-2(1H)-oneYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent5×

Conditions

Temperature
70 °C

Procedure

A 28% solution of sodium methoxide in methanol (14 μL) was added to a solution of 3-cyclopropyl-6-{(E)-1-[3-fluoro-4-(methylsulfonyl)phenyl]-2-[(2R)-5-oxopyrrolidin-2-yl]ethenyl}pyridin-2(1H)-one obtained in Example 4-386 (10 mg) in methanol (0.5 mL), after which the mixture was stirred at 70° C. for 30 minutes. The reaction solution was left to cool to room temperature. 3-Cyclopropyl-6-{(E)-1-[3-fluoro-4-(methylsulfonyl)phenyl]-2-[(2R)-5-oxopyrrolidin-2-yl]ethenyl}pyridin-2(1H)-one (50 mg), methanol (3 mL) and a 28% solution of sodium methoxide in methanol (80 μL) were then added, after which the mixture was stirred at 70° C. for two hours. The reaction solution was left to cool to room temperature and a 28% solution of sodium methoxide in methanol (1 mL) was then added, after which the mixture was stirred at 70° C. for one hour. The reaction solution was left to cool to room temperature, and water was then added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by NH-silica gel column chromatography (methanol:ethyl acetate=1:10) to give the title compound as a pale yellow solid (40 mg, 65%).

Workup

  1. waitThe reaction solution was left
  2. temperatureto cool to room temperature
  3. stirringafter which the mixture was stirred at 70° C. for two hours
  4. waitThe reaction solution was left
  5. temperatureto cool to room temperature
  6. stirringafter which the mixture was stirred at 70° C. for one hour
  7. waitThe reaction solution was left
  8. temperatureto cool to room temperature
  9. extractionfollowed by extraction with ethyl acetate
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. customafter which the solvent was evaporated under reduced pressure
  14. customThe residue was purified by NH-silica gel column chromatography (methanol:ethyl acetate=1:10)

Sources & evidence

ORD record
ord-fec6e5c393ec430c815c3ea046d16bf1
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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