Methyl iodide → 4-[[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino]-5-methylfuran-2(5H)-one

HRID 1952252Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:16][CH:17]([F:19])[F:18])[C:10]2[CH2:14][O:13][C:12](=[O:15])[CH:11]=2)=[CH:4][CH:3]=1.[C:20]([Li])(C)(C)C.CI>O1CCCC1.CCCCC>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:16][CH:17]([F:19])[F:18])[C:10]2[CH:14]([CH3:20])[O:13][C:12](=[O:15])[CH:11]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

300 mg (1.04 mmol) of 4-[[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino]furan-2(5H)one (1) are dissolved in 10 ml of tetrahydrofuran, the solution is cooled to −78° C. and 611 μl (1.04 mmol) of a 1.7 M solution of tert.-butyllithium in pentane are added. After 30 min of stirring at −78° C., 65 μl (1.04 mmol) of methyl iodide are added, stirring is continued at −78° C. for a further 30 min and the mixture is warmed to room temperature. Concentration under reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (2:1) gives 152 mg (47% of theory) of 4-[[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino]-5-methylfuran-2(5H)-one.

Workup

stirringstirring
waitis continued at −78° C. for a further 30 min
temperaturethe mixture is warmed to room temperature
concentrationConcentration
customunder reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record: ord-e86b5e90037648f6bf1d932997130516
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404855B2

Reaction notes

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