Acetonitrile → 4-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]-1-propylpiperazine-2,6-dione

HRID 63854Notes

Reaction equation

HRID 63854 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:37]([F:40])([F:39])[F:38])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:30][C:29](=[O:31])[NH:28][C:27](=[O:32])[CH2:26]4)=[O:24])=[C:19]([C:33]([F:36])([F:35])[F:34])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.I[CH2:42][CH2:43][CH3:44].C(=O)([O-])[O-].[K+].[K+].CC#N>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:37]([F:40])([F:38])[F:39])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:26][C:27](=[O:32])[N:28]([CH2:42][CH2:43][CH3:44])[C:29](=[O:31])[CH2:30]4)=[O:24])=[C:19]([C:33]([F:36])([F:35])[F:34])[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 6342AcetonitrileHCID 11430Potassium CarbonateHCID 336431-IodopropaneHCID 1180467104-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]piperazine-2,6-dione

Product 1

HCID 1180472874-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]-1-propylpiperazine-2,6-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Into a 25-mL round-bottom flask, was placed a solution of 4-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]piperazine-2,6-dione (70 mg, 0.12 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL), 1-iodopropane (32 mg, 0.19 mmol, 2.00 equiv), potassium carbonate (59 mg, 0.43 mmol, 3.00 equiv). The resulting solution was stirred for 2 h at 25° C. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×10 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 31 mg (41%) of 4-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]-1-propylpiperazine-2,6-dione as a white solid. (ES, m/z): [M+CH3CN]+ 685.0; 1H NMR (300 MHz, CDCl3): δ 7.79-7.84 (m, 2H), 7.73-7.87 (m, 3H), 7.46 (d, J=7.8 Hz, 1H), 4.86 (d, J=19.4 Hz, 1H), 4.56 (d, J=18.3 Hz, 1H), 4.19 (d, J=17.4 Hz, 1H), 4.05 (s, 2H), 3.75-3.81 (m, 3H), 1.52-1.64 (m, 2H), 0.93 (t, J=7.2 Hz, 3H).

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. customThe reaction was then quenched by the addition of 10 mL of water
  3. extractionThe resulting solution was extracted with 2×10 mL of ethyl acetate
  4. concentrationconcentrated under vacuum
  5. customThis resulted in 31 mg (41%) of 4-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]-1-propylpiperazine-2,6-dione as a white solid

Sources & evidence

ORD record
ord-f5db62a76a9a4497862d082cc6bfad86
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

Loading…