Dimethylformamide → Methyl 2-(3-((4-(difluoromethyl)phenyl)difluoromethyl)-2-oxoimidazolidin-1-yl)isonicotinate

HRID 714285Notes

Reaction equation

HRID 714285 reaction equation
[O:1]=[C:2]1[NH:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=1)[C:10]([O-:12])=[O:11].[H-].[Na+].Br[C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][C:23]([CH:26]([F:28])[F:27])=[CH:22][CH:21]=1.[CH3:31]N(C)C=O>>[F:29][CH:19]([F:30])[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:28])([F:27])[N:6]2[CH2:5][CH2:4][N:3]([C:7]3[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=3)[C:10]([O:12][CH3:31])=[O:11])[C:2]2=[O:1])=[CH:22][CH:21]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27788231-(Bromodifluoromethyl)-4-(difluoromethyl)benzene2×HCID 866530512-(2-Oxoimidazolidin-1-yl)isonicotinate

Product 1

HCID 58247774Methyl 2-(3-((4-(difluoromethyl)phenyl)difluoromethyl)-2-oxoimidazolidin-1-yl)isonicotinateYield 13%

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(2-oxoimidazolidin-1-yl)isonicotinate (0.50 g, 2.26 mmol) in N,N-dimethylformamide (15 mL) was added sodium hydride (0.10 g, 60% dispersion in mineral oil, 2.5 mmol) at 0° C. The resulting solution was stirred at 0° C. for 30 minutes, followed by the addition of 1-(bromodifluoromethyl)-4-(difluoromethyl)benzene (0.58 g, 2.26 mmol). The mixture was warmed to ambient temperature and stirred for 55 hours. 1-(Bromodifluoromethyl)-4-(difluoromethyl)benzene (0.13 g, 0.5 mmol) was again added and the reaction was stirred at 60° C. for 5 hours then concentrated in vacuo to dryness. The residue was purified by column chromatography eluting with hexanes and ethyl acetate (from 10:1 to 1:1) to give methyl 2-(3-((4-(difluoromethyl)phenyl)-difluoromethyl)-2-oxoimidazolidin-1-yl)isonicotinate as a colorless solid (0.09 g, 13%): MS (ES+) m/z 397.8 (M+1).

Workup

  1. temperatureThe mixture was warmed to ambient temperature
  2. stirringstirred for 55 hours
  3. stirringthe reaction was stirred at 60° C. for 5 hours
  4. concentrationthen concentrated in vacuo to dryness
  5. customThe residue was purified by column chromatography
  6. washeluting with hexanes and ethyl acetate (from 10:1 to 1:1)

Sources & evidence

ORD record
ord-4ddb40b2a53a440a89378555de0ff263
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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