Triethylamine → 5-[3,5-Bis(trifluoromethyl)phenyl]-3-(4-bromo-1-naphthalenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole

HRID 1958876Notes

Reaction equation

HRID 1958876 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.[F:23][C:24]([F:42])([F:41])[C:25]1[CH:30]=[C:29]([C:31]([C:33]([F:36])([F:35])[F:34])=[CH2:32])[CH:28]=[C:27]([C:37]([F:40])([F:39])[F:38])[CH:26]=1.C(N(CC)CC)C>CN(C)C=O.O>[F:23][C:24]([F:41])([F:42])[C:25]1[CH:30]=[C:29]([C:31]2([C:33]([F:36])([F:35])[F:34])[O:22][N:21]=[C:20]([C:13]3[C:14]4[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:10]([Br:9])=[CH:11][CH:12]=3)[CH2:32]2)[CH:28]=[C:27]([C:37]([F:38])([F:39])[F:40])[CH:26]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 498208821,3-Bis(trifluoromethyl)-5-(1,1,1-trifluoroprop-2-en-2-yl)benzeneHCID 74016047(E)-4-bromo-1-naphthaldehyde oxime2×

Product 1

HCID 866462125-[3,5-Bis(trifluoromethyl)phenyl]-3-(4-bromo-1-naphthalenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

N-Chlorosuccinimide (2.05 g, 15.5 mmol) was added to a solution of 4-bromo-1-naphthalenecarboxaldehyde oxime (i.e. the product of Example 4, Step A, 3.20 g, 12.8 mmol) in N,N-dimethylformamide (20.0 mL). The reaction mixture was stirred for 1 h at room temperature, and then a solution of 1,3-bis(trifluoromethyl)-5-[1-(trifluoromethyl)ethenyl]benzene (5.13 g, 16.6 mmol, prepared according to the method described in J. Org. Chem. 1959, 24, 238-239) and triethylamine (5.4 mL, 38.4 mmol) in N,N-dimethylformamide (10.0 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 (3.2 g). 1H NMR (CDCl3): δ 8.89 (m, 1H), 8.35 (m, 1H), 8.13 (s, 2H), 7.99 (s, 1H), 7.81 (d, 1H), 7.69 (m, 2H), 7.37 (d, 1H), 4.38 (d, 1H), 3.94 (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-fbfa313488cb414593217dd38f253876
Source dataset
uspto-grants-2013_04
Patent number
US08410153B2

Reaction notes

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