Triethylamine → 3-(4-Bromo-1-naphthalenyl)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole

HRID 1958873Notes

Reaction equation

HRID 1958873 reaction equation
ClN1C(=O)CCC1=O.[Br:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH:20]=[N:21][OH:22])=[CH:12][CH:11]=1.[Cl:23][C:24]1[CH:29]=[C:28]([C:30]([C:32]([F:35])([F:34])[F:33])=[CH2:31])[CH:27]=[C:26]([Cl:36])[CH:25]=1.BrC(C(F)(F)F)=C.FF.C(N(CC)CC)C>CN(C)C=O.O>[Br:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([C:20]2[CH2:31][C:30]([C:28]3[CH:27]=[C:26]([Cl:36])[CH:25]=[C:24]([Cl:23])[CH:29]=3)([C:32]([F:33])([F:35])[F:34])[O:22][N:21]=2)=[CH:12][CH:11]=1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 24524FluorineHCID 31398ChlorosuccinimideHCID 2726961-Propene, 2-bromo-3,3,3-trifluoro-HCID 231598231,3-Dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 74016047(E)-4-bromo-1-naphthaldehyde oxime2×

Product 1

HCID 866452773-(4-Bromo-1-naphthalenyl)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

N-Chlorosuccinimide (1.70 g, 12.7 mmol) was added to a solution of 4-bromo-1-naphthalenecarboxaldehyde oxime (i.e. the product of Step A, 2.33 g, 9.3 mmol) in N,N-dimethylformamide (6.0 mL). The reaction mixture was stirred for 1 h at room temperature, and then a solution of 1,3-dichloro-5-[1-(trifluoromethyl)ethenyl]benzene (2.70 g, 11.2 mmol, prepared from commercially available 2-bromo-3,3,3-trifluoropropene by the method described in J. Fluorine Chem. 1999, 95, 167-170) and triethylamine (4.5 mL, 32.0 mmol) in N,N-dimethylformamide (9.0 mL) was added. After stirring for an additional 2 h at room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluted with ethyl acetate/hexanes to afford the title compound as a white solid (2.9 g). 1H NMR (CDCl3): δ 8.87 (m, 1H), 8.32 (m, 1H), 7.77 (d, 1H), 7.66 (m, 2H), 7.55 (s, 1H), 7.46 (dd, 1H), 7.32 (d, 1H), 4.24 (d, 1H), 3.88 (d, 3H).

Workup

  1. stirringAfter stirring for an additional 2 h at room temperature
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel
  8. washeluted with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-08bcd5b13ede49c6a200818fbba1d3f1
Source dataset
uspto-grants-2013_04
Patent number
US08410153B2

Reaction notes

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