反应详情

To a mixture of magnesium turnings (0.17 g, 6.98 mmol) and 1,2-dibromoethane (2 drops) in tetrahydrofuran (0.5 mL) under a nitrogen atmosphere was added dropwise a solution of 3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole (i.e. the product of Step C) (2.0 g, 5.25 mmol) in tetrahydrofuran (3.5 mL). After about 2% of the total volume of the 3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole solution had been added, the addition was stopped and iodine (catalytic amount) was added to the reaction mixture. The remaining 3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)-phenyl]-1H-pyrazole solution was then added to the reaction mixture over 1 h while heating at reflux. Heating was continued for an additional 45 minutes, and then the reaction mixture was cooled to room temperature. The reaction mixture was added via an addition funnel to a solution of oxalyl chloride (0.508 mL, 5.82 mmol) in tetrahydrofuran (6 mL) at −65° C. Stirring was continued for 2 h at −65° C., and then methanol (1.17 mL) was added to the reaction mixture, and the mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was diluted with saturated aqueous ammonium chloride (4 mL) and water (8 mL) and then extracted with ethyl acetate (2×). The combined organic layers were washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give an oil. The oil was purified by medium pressure liquid chromatography (0 to 20% gradient of ethyl acetate in hexanes as eluant) to provide an oil (0.31 g). The oil was crystallized from hexanes-diethyl ether to provide the title compound, a compound of the present invention, as a solid (200 mg).

1. additionthe addition
2. temperaturewhile heating
3. temperatureat reflux
4. temperatureHeating
5. waitwas continued for 2 h at −65° C.
6. temperatureto warm to room temperature
7. stirringstirred for 2 h
8. extractionextracted with ethyl acetate (2×)
9. washThe combined organic layers were washed with saturated aqueous sodium chloride
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customto give an oil
14. customThe oil was purified by medium pressure liquid chromatography (0 to 20% gradient of ethyl acetate in hexanes as eluant)