反应详情

To a solution of 4-(hydroxyimino-methyl)-2-methyl-benzoic acid tert-butyl ester (Example I18) (32.5 g) in N,N-dimethylformamide (280 ml) was added N-chlorosuccinimide (“NCS”) (18.44 g). The reaction mixture was stirred at ambient temperature for 3.5 hour. A solution of 1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (33.3 g) (prepared according to WO 2005/085216) and triethylamine (19.25 ml) in N,N-dimethylformamide (220 ml) was added dropwise to the reaction mixture. The reaction mixture was stirred at ambient temperature for 16 hours. Water and ethyl acetate were added and the phases were separated. The organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was crystallized from ethyl acetate and heptane to give 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid tert-butyl ester (40.12 g). 1H-NMR (CDCl3, 400 MHz): 7.88 (d, 1H), 7.55-7.45 (m, 5H), 4.10 (d, 1H), 3.75 (d, 1H), 2.60 (s, 3H), 1.65 (s, 9H).

1. stirringThe reaction mixture was stirred at ambient temperature for 16 hours
2. customthe phases were separated
3. washThe organic layer was washed with water
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. customThe residue was crystallized from ethyl acetate and heptane