Methyl iodide → 4-(2-Fluoropyridin-3-yl)-1-methylpyrrolidin-2-one

HRID 410266Notes

Reaction equation

HRID 410266 reaction equation
[F:1][C:2]1[C:7]([CH:8]2[CH2:12][NH:11][C:10](=[O:13])[CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.I[CH3:15].[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[C:7]([CH:8]2[CH2:12][N:11]([CH3:15])[C:10](=[O:13])[CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59326922HCID 59326922, compound

Product 1

HCID 593270184-(2-Fluoropyridin-3-yl)-1-methylpyrrolidin-2-oneYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(2-fluoropyridin-3-yl)pyrrolidin-2-one (0.254 g, 1.41 mmol) in DMF (5 mL) at 0° C. was added iodomethane (0.090 mL, 1.4 mmol) and sodium hydride (60% weight dispersion in mineral oil, 0.056 g, 1.4 mmol). The reaction mixture was stirred at 0° C. for 30 min, warmed to room temperature, and stirred for 30 min. The reaction mixture was diluted with EtOAc, quenched with water, and diluted with brine and water. The aqueous phase was extracted with EtOAc (6×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (50% to 100% EtOAc (10% MeOH) in hexanes) gave 4-(2-fluoropyridin-3-yl)-1-methylpyrrolidin-2-one (0.226 g, 1.16 mmol, 83% yield) as a pale yellow oil. MS (ESI, pos. ion) m/z: 195.1 (M+1).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for 30 min
  3. customquenched with water
  4. additiondiluted with brine and water
  5. extractionThe aqueous phase was extracted with EtOAc (6×)
  6. washthe combined organic extracts were washed with brine (1×)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography on silica gel (50% to 100% EtOAc (10% MeOH) in hexanes)

Sources & evidence

ORD record
ord-e4a29e2e60ce475f9a26434861d11914
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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