Dimethylformamide → 1-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one

HRID 63841Notes

Reaction equation

HRID 63841 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:32]([F:35])([F:34])[F:33])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:29][C:28](=[O:30])[NH:27][CH2:26]4)=[O:24])=[C:19]([CH3:31])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CN(C)C=O.[H-].[Na+].FC(F)(F)S(O[CH2:49][C:50]([F:53])([F:52])[F:51])(=O)=O>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:32]([F:33])([F:34])[F:35])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:29][C:28](=[O:30])[N:27]([CH2:49][C:50]([F:53])([F:52])[F:51])[CH2:26]4)=[O:24])=[C:19]([CH3:31])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 1180467971-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one

Product 1

HCID 1180468891-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one (80 mg, 0.15 mmol, 1.00 equiv), N,N-dimethylformamide (5 mL). This was followed by the addition of NaH (60%) (12.3 mg, 0.51 mmol, 2.00 equiv) in several batches at 0° C. The resulting solution was stirred for 30 min at 0° C. To this was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (71 mg, 0.31 mmol, 2.00 equiv). The resulting solution was allowed to react, with stirring, for an additional 3 h at room temperature. The reaction was then quenched by the addition of 20 mL of water/ice. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined. The mixture was dried over anhydrous sodium sulfate. This resulted in 14 mg (15%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one as a light yellow solid. (ES, m/z): [M+CH3CN]+ 643; 1H NMR (300 MHz, CDCl3): δ 7.82 (s, 1H), 7.76 (s, 1H), 7.697 (s, 1H), 7.58-7.61 (m, 2H), 7.28-7.34 (m, 1H), 5.196 (s, 1H), 4.911 (s, 1H), 4.646 (s, 1H), 4.03-4.18 (m, 2H), 3.998 (s, 1H), 3.70-3.76 (m, 1H), 2.399 (s, 3H).

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customto react
  4. stirringwith stirring, for an additional 3 h at room temperature
  5. customThe reaction was then quenched by the addition of 20 mL of water/ice
  6. extractionThe resulting solution was extracted with 3×10 mL of ethyl acetate
  7. dry with materialThe mixture was dried over anhydrous sodium sulfate
  8. customThis resulted in 14 mg (15%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one as a light yellow solid

Sources & evidence

ORD record
ord-0097cec0a88749728d6d09eaa86d763d
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

Loading…