反应详情

A mixture of 500 mg (2.15 mmol) of ethyl 3-amino-4-(trifluoromethyl)benzoate (from Step D) and 5 mL of concentrated hydrochloric acid was stirred at 0°-5° C. as a cold solution of 173 mg (2.50 mmol) of sodium nitrite in 0.8 mL of H2O was added. After being stirred at 0°-5° C. for 1 hour, the mixture was filtered while cold, and the filtrate was poured into a solution of 1.02 g (4.5 mmol) of stannous chloride dihydrate in 2 mL of concentrated hydrochloric acid stirred at 0° C. Precipitation occurred immediately. The mixture was kept in an ice bath for 1.5 hours, and then the solid was collected by filtration. The solid is dried to yield the title compound suitable for use in the pyrazole ring formation reaction. In this experiment, the material was characterized as the free base by partitioning the solid hydrochloride between 2N Na2CO3 (aqueous) and ethyl acetate. The ethyl acetate phase was washed with brine, dried, filtered, and concentrated to yield 375 mg (70%) of the free base of the title compound as a pale yellow oil; homogeneous by TLC in 4:1 hexane-EtOAc and 98:2 CH2Cl2 --MeOH. 200 MHz 1H NMR (CD3OD) for free base: δ1.38 (t, J=7.1 Hz, 3H), 4.36 (q, J=7.1 Hz, 2H), 7.34 (d, J=8 Hz, 1H), 7.48 (d, J= 8 Hz, 1H), 8.05 (s, 1H).

1. additionwas added
2. filtrationthe mixture was filtered while cold, and the filtrate
3. stirringstirred at 0° C
4. customPrecipitation
5. waitThe mixture was kept in an ice bath for 1.5 hours
6. filtrationthe solid was collected by filtration
7. customThe solid is dried