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

HRID 1880132Notes

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

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

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

Sources & evidence

ORD record: ord-4f7b4681fe4747f996be81f4e473dbdb
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318718B2

Reaction notes

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