Sodium hydride → 1-([4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-3-(2,2,2-trifluoroethyl)imidazolidin-4-one

HRID 63850Notes

Reaction equation

HRID 63850 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:32]([F:35])([F:34])[F:33])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([N:22]4[CH2:26][C:25](=[O:27])[NH:24][CH2:23]4)=[O:21])=[C:16]([C:28]([F:31])([F:30])[F:29])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[H-].[Na+].FC(F)(F)S(O[CH2:44][C:45]([F:48])([F:47])[F:46])(=O)=O>CN(C)C=O.[Cl-].[Na+].O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:32]([F:33])([F:35])[F:34])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([N:22]4[CH2:26][C:25](=[O:27])[N:24]([CH2:44][C:45]([F:48])([F:47])[F:46])[CH2:23]4)=[O:21])=[C:16]([C:28]([F:31])([F:30])[F:29])[CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 1180472501-([4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)imidazolidin-4-one

Product 1

HCID 1180473781-([4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-3-(2,2,2-trifluoroethyl)imidazolidin-4-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
20 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)imidazolidin-4-one (300 mg, 0.56 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), sodium hydride (26 mg, 1.08 mmol, 2.00 equiv), 2,2,2-trifluoroethyl trifluoromethanesulfonate (260 mg, 1.12 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at 20° C. The resulting solution was diluted with 50 mL of brine. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined and dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/5). This resulted in 58.8 mg (17%) of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-3-(2,2,2-trifluoroethyl)imidazolidin-4-one as a off-white solid. (ES, m/z): [M−H]− 620; 1H NMR (300 MHz, CDCl3) δ: 8.01-8.03 (m, 2H), 7.53 (s, 3H), 7.47 (s, 1H), 5.20 (s, 1H), 4.65 (s, 1H), 4.32 (s, 1H), 4.17 (s, 1H), 4.02-4.11 (m, 2H), 3.73-3.84 (m, 2H)

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. extractionThe resulting solution was extracted with 3×50 mL of ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThis resulted in 58.8 mg (17%) of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-3-(2,2,2-trifluoroethyl)imidazolidin-4-one as a off-white solid

Sources & evidence

ORD record
ord-3544437a0b17445eba81d2b89eed4120
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

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