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

HRID 63875Notes

Reaction equation

HRID 63875 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]([OH:23])=O)=[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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH:65]1[CH2:69][C:68](=[O:70])[NH:67][CH2:66]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:27]([F:30])([F:28])[F:29])[O:16][N:15]=[C:14]([C:17]3[CH:25]=[CH:24][C:20]([C:21]([N:65]4[CH2:69][C:68](=[O:70])[NH:67][CH2:66]4)=[O:23])=[C:19]([CH3:26])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56965782Imidazolidin-4-one hydrochlorideHCID 867316494-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid

Product 1

HCID 1180467971-[(4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (900 mg, 1.99 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (1.1 g, 2.89 mmol, 1.45 equiv), DIEA (770 mg, 5.96 mmol, 2.99 equiv), imidazolidin-4-one hydrochloride (489 mg, 3.99 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at rt. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting organic phase was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/30-1/10). This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid.

Workup

  1. customInto a 100-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 3×10 mL of ethyl acetate
  4. washThe resulting mixture was washed with 3×20 mL of brine
  5. concentrationThe resulting organic phase was concentrated under vacuum
  6. customThis resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid

Sources & evidence

ORD record
ord-e4124c1a7100499ba282f5191077780a
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

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