Triethylamine → Methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

HRID 1958868Notes

Reaction equation

HRID 1958868 reaction equation
ClN1C(=O)CCC1=O.[OH:9][N:10]=[CH:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([C:22]([O:24][CH3:25])=[O:23])=[CH:14][CH:13]=1.[Cl:26][C:27]1[CH:32]=[C:31]([C:33]([C:35]([F:38])([F:37])[F:36])=[CH2:34])[CH:30]=[C:29]([Cl:39])[CH:28]=1.BrC(C(F)(F)F)=C.FF.C(N(CC)CC)C>CN(C)C=O.O>[Cl:26][C:27]1[CH:32]=[C:31]([C:33]2([C:35]([F:38])([F:36])[F:37])[O:9][N:10]=[C:11]([C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15]([C:22]([O:24][CH3:25])=[O:23])=[CH:14][CH:13]=3)[CH2:34]2)[CH:30]=[C:29]([Cl:39])[CH:28]=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 86645276Methyl 4-[(hydroxyimino)methyl]-1-naphthalenecarboxylate2×

Product 1

HCID 58338637Methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

N-Chlorosuccinimide (1.16 g, 8.72 mmol) was added to a stirred solution of methyl 4-[(hydroxyimino)methyl]-1-naphthalenecarboxylate (i.e. the product of Step A, 1.0 g, 4.36 mmol) in N,N-dimethylformamide (5.0 mL). This mixture was stirred for 1.5 h at room temperature, and then a solution of 1,3-dichloro-5-[1-(trifluoromethyl)ethenyl]benzene (3.20 g, 13.1 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 (6.1 mL, 43.6 mmol) in N,N-dimethylformamide (4.0 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 combined organic extracts were 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 pale yellow oil (700 mg). 1H NMR (CDCl3): δ 8.88 (d, 1H), 8.80 (d, 1H), 8.10 (d, 1H), 7.68 (m, 2H), 7.55 (m, 3H), 7.46 (dd, 1H), 4.27 (d, 1H), 4.03 (s, 3H), 3.91 (d, 1H).

Workup

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

Sources & evidence

ORD record
ord-538a485944f14f25868bc17399a645b0
Source dataset
uspto-grants-2013_04
Patent number
US08410153B2

Reaction notes

Loading…