Potassium Carbonate → 4-([4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-1-(2,2,2-trifluoroethyl)piperazine-2,6-dione

HRID 63848Notes

Reaction equation

HRID 63848 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:34]([F:37])([F:36])[F:35])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([N:22]4[CH2:27][C:26](=[O:28])[NH:25][C:24](=[O:29])[CH2:23]4)=[O:21])=[C:16]([C:30]([F:33])([F:32])[F:31])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C([O-])([O-])=O.[K+].[K+].FC(F)(F)S(O[CH2:50][C:51]([F:54])([F:53])[F:52])(=O)=O>CN(C)C=O.[Cl-].[Na+].O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:34]([F:35])([F:37])[F:36])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([N:22]4[CH2:23][C:24](=[O:29])[N:25]([CH2:50][C:51]([F:54])([F:53])[F:52])[C:26](=[O:28])[CH2:27]4)=[O:21])=[C:16]([C:30]([F:33])([F:32])[F:31])[CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 1180471824-([4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)piperazine-2,6-dione

Product 1

HCID 1180471124-([4-[5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-1-(2,2,2-trifluoroethyl)piperazine-2,6-dione

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 4-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)piperazine-2,6-dione (300 mg, 0.53 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), K2CO3 (140 mg, 1.01 mmol, 2.00 equiv), 2,2,2-trifluoroethyl trifluoromethanesulfonate (240 mg, 1.03 mmol, 2.00 equiv). The resulting solution was stirred for 1 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. The mixture was 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 235.9 mg (69%) of 4-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-1-(2,2,2-trifluoroethyl)piperazine-2,6-dione as a off-white solid. (ES, m/z): [M−H]− 648; 1H NMR (300 MHz, CDCl3) δ: 8.00-8.05 (m, 2H), 7.44-7.53 (m, 4H), 4.94-5.01 (m, 1H), 4.68 (s, 1H), 4.50-4.56 (m, 2H), 4.10-4.16 (m, 3H), 3.76 (d, J=17.4 Hz, 1H)

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 materialThe mixture was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThis resulted in 235.9 mg (69%) of 4-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)-1-(2,2,2-trifluoroethyl)piperazine-2,6-dione as a off-white solid

Sources & evidence

ORD record
ord-e1f848eb848d482caddb90e3c97e043a
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

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