Bromine → (5R)-5-[(Z)-2-bromo-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

HRID 70538Notes

Reaction equation

HRID 70538 reaction equation
[Br:1]Br.[Cl:3][C:4]1[CH:5]=[CH:6][C:7](/[CH:12]=[CH:13]\[C@@H:14]2[NH:18][C:17](=[O:19])[CH2:16][CH2:15]2)=[N:8][C:9]=1[O:10][CH3:11]>C(Cl)(Cl)(Cl)Cl>[Br:1]/[C:12](/[C:7]1[CH:6]=[CH:5][C:4]([Cl:3])=[C:9]([O:10][CH3:11])[N:8]=1)=[CH:13]\[C@@H:14]1[NH:18][C:17](=[O:19])[CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 24408BromineHCID 58452452HCID 58452452, compound

Product 1

HCID 58452317(5R)-5-[(Z)-2-bromo-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-oneYield 62%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
0 °C

Procedure

Bromine (80 μL) was added to a solution of (5R)-5-[(Z)-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one (200 mg) in carbon tetrachloride (2 mL) under ice-cooling, and the mixture was stirred at the same temperature (0° C.) for 15 minutes. The reaction solution was concentrated and the residue was dissolved in chloroform. 1,8-Diazabicyclo[5.4.0]undec-7-ene (238 μL) was added under ice-cooling, and the mixture was stirred at room temperature for one hour. 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 silica gel column chromatography (hexane:ethyl acetate=1:1→0:1) to give the title compound as a colorless powder (164 mg, 62%).

Workup

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated
  3. dissolutionthe residue was dissolved in chloroform
  4. addition1,8-Diazabicyclo[5.4.0]undec-7-ene (238 μL) was added under ice-
  5. temperaturecooling
  6. stirringthe mixture was stirred at room temperature for one hour
  7. additionThe reaction solution was poured into water
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customThe solvent was then evaporated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1)

Sources & evidence

ORD record
ord-9d00c36e428e44e29b5afc0b58935db0
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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