Dimethylformamide → 2-Amino-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzonitrile

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Reaction Conditions

Reaction Steps

To a solution of 2-bromo-5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenylamine (Example I3) (0.840 g, 1.84 mmol) in N,N-dimethylformamide (3 ml) under a nitrogen atmosphere was added zinc(II) cyanide (0.346 g, 2.94 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.255 g, 0.22 mmol). The reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was diluted with toluene and the phases were separated. The aqueous phase was extracted twice with toluene. The combined organic phases were washed with brine and aqueous ammonium hydroxide (saturated), dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:5) to give 2-amino-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzonitrile (0.480 g, 36% yield). 1H-NMR (CDCl3, 400 MHz): 7.45 (m, 4H), 7.08 (s, 1H), 6.95 (q, 1H), 4.52 (s, 2H), 4.02 (d, 1H), 3.62 (d, 1H).

Provenance & Evidence