1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]piperazine-2,6-dione

HRID 63843Notes

Reaction equation

HRID 63843 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:27]([F:30])([F:29])[F:28])[O:16][N:15]=[C:14]([C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[C:19]([CH3:26])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH:52]1[C:57](=[O:58])[CH2:56][NH:55][CH2:54][C:53]1=[O:59]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:27]([F:28])([F:29])[F:30])[O:16][N:15]=[C:14]([C:17]3[CH:25]=[CH:24][C:20]([C:21]([N:55]4[CH2:56][C:57](=[O:58])[NH:52][C:53](=[O:59])[CH2:54]4)=[O:22])=[C:19]([CH3:26])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 338690Piperazine-2,6-dioneHCID 867316494-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid

Product 1

HCID 1180473454-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]piperazine-2,6-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a 100-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (452 mg, 1.00 mmol, 1.00 equiv), dichloromethane (50 mL), TEA (202 mg, 2.00 mmol, 2.00 equiv), EDCI (384 mg, 2.00 mmol, 2.00 equiv), HOBt (270 mg, 2.00 mmol, 2.00 equiv). The mixture was stirred for 0.5 h at room temperature. This was followed by the addition of piperazine-2,6-dione (125 mg, 1.10 mmol, 1.10 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 3×50 mL of brine. The mixture was dried over anhydrous sodium sulfate. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 210 mg (38%) of 4-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]piperazine-2,6-dione as a light yellow solid.

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred overnight at room temperature
  3. washThe resulting mixture was washed with 3×50 mL of brine
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. customThis resulted in 210 mg (38%) of 4-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]piperazine-2,6-dione as a light yellow solid

Sources & evidence

ORD record
ord-e5a29fbec72a490eb6ba67c76388e9ee
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

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