Triethylamine → 4-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

HRID 1037018Notes

Reaction equation

HRID 1037018 reaction equation
Cl[C:2](=[N:13][OH:14])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([CH3:12])[CH:4]=1.[Cl:15][C:16]1[CH:21]=[C:20]([C:22]([C:24]([F:27])([F:26])[F:25])=[CH2:23])[CH:19]=[C:18]([Cl:28])[C:17]=1[F:29].CCN(CC)CC.CC(=O)OCC>CN(C=O)C.CC(=O)OCC.CO>[Cl:15][C:16]1[CH:21]=[C:20]([C:22]2([C:24]([F:27])([F:26])[F:25])[O:14][N:13]=[C:2]([C:3]3[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([CH3:12])[CH:4]=3)[CH2:23]2)[CH:19]=[C:18]([Cl:28])[C:17]=1[F:29]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 584682331,3-Dichloro-2-fluoro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 86685466HCID 86685466, compound

Product 1

HCID 866854534-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acidYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of 4-(chloro(hydroxyimino)methyl)-2-methylbenzoic acid (5.1 g, 23.8 mmol) in DMF (30 mL) at 0° C. was added 1,3-dichloro-2-fluoro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (7.4 g, 28.6 mmol) followed by Et3N (4.8 g, 47.6 mmol). The reaction mixture was stirred at rt for 18 h, poured into ice-water (30 mL) and extracted with ethyl acetate (60 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (1:1) to EA: MeOH (10:1) to give 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (6 g; yield 58% over 3 steps) as a white solid. MS: m/z=435.8 (M+1, ESI+).

Workup

  1. extractionextracted with ethyl acetate (60 mL×3)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography over silica gel
  7. washeluted with PE

Sources & evidence

ORD record
ord-abe7fcca9e1941a1bbb37ef27692846f
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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