反应详情

温度

60 °C

To a solution of N-{6-[4-methyl-3-(trifluoromethoxy)phenoxy]pyridin-3-yl}acetamide (Intermediate 32, 500 mg, 1.53 mmol) in 2.2 mL of POCl3, methyl carbazate (152 mg) was added. The resulting mixture was heated at 60° C. for 7 hrs and overnight at room temperature. After additional heating for 5 hrs, further methyl carbazate (30 mg, 0.2 equiv) was added. The mixture was cooled to 0° C. and water was cautiously added, followed by a saturated solution of K2CO3 and then solid K2CO3 until pH=8 was reached. Ethyl acetate (50 mL) was then added and phases were separated. The aqueous phase was then back-extracted with ethyl acetate (2×50 mL). The combined organics were dried over Na2SO4, filtered and concentrated to give 520 mg of crude as orange foam which was purified by silica flash-chromatography, eluant cyclohexane/ethyl acetate, gradient from 50/50 to 20/80 v/v giving the title compound (360 mg) as white foam.

1. temperatureAfter additional heating for 5 hrs
2. temperatureThe mixture was cooled to 0° C.
3. customphases were separated
4. extractionThe aqueous phase was then back-extracted with ethyl acetate (2×50 mL)
5. dry with materialThe combined organics were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give 520 mg of crude as orange foam which
9. customwas purified by silica flash-chromatography, eluant cyclohexane/ethyl acetate, gradient from 50/50 to 20/80 v/v