Methyl iodide → 5-[2-(4-bromo-2-chloro-phenyl)-propionyl]-1-methyl-1H-pyridin-2-one

HRID 1095984Notes

Reaction equation

HRID 1095984 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:11]2[CH:12]=[CH:13][C:14](=[O:18])[N:15]([CH3:17])[CH:16]=2)=[O:10])=[C:4]([Cl:19])[CH:3]=1.[H-].[Na+].[CH3:22]I>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:22])[C:9]([C:11]2[CH:12]=[CH:13][C:14](=[O:18])[N:15]([CH3:17])[CH:16]=2)=[O:10])=[C:4]([Cl:19])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 666994925-[2-(4-bromo-2-chloro-phenyl)-acetyl]-1-methyl-1H-pyridin-2-one

Product 1

HCID 666994195-[2-(4-bromo-2-chloro-phenyl)-propionyl]-1-methyl-1H-pyridin-2-oneYield 58.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of the 5-[2-(4-bromo-2-chloro-phenyl)-acetyl]-1-methyl-1H-pyridin-2-one obtained in step 1 (583 mg) in tetrahydrofuran (12 ml) was added sodium hydride (60% dispersion in mineral oil, 72 mg). The mixture was stirred at room temperature for 2 h and at 40° C. for 30 min. The mixture was cooled in an ice bath. Methyl iodide (267 mg) was added dropwise. After 10 min the ice bath was removed and the mixture was stirred at room temperature for 4 h. Sodium hydride (60% dispersion in mineral oil, 35 mg) and methyl iodide (121 mg) were added and the mixture was stirred overnight at room temperature. The reaction was quenched with ice water and extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 7:3=>0:1) to give the title compound (353 mg) as a colorless foam. MS (m/e, ISP neg. ion)=352.0 [M−H+].

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customAfter 10 min the ice bath was removed
  3. stirringthe mixture was stirred at room temperature for 4 h
  4. additionSodium hydride (60% dispersion in mineral oil, 35 mg) and methyl iodide (121 mg) were added
  5. stirringthe mixture was stirred overnight at room temperature
  6. customThe reaction was quenched with ice water
  7. extractionextracted with EtOAc
  8. dry with materialThe organic phase was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 7:3=>0:1)

Sources & evidence

ORD record
ord-845f1851df724f7a98a8e04f9e5fb77c
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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