反应详情

温度

0 °C

A solution of triphenylphosphine (341 mg, 1.3 mmol) in methylene chloride (7 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (231 mg, 1.3 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with (E)-3-cycloheptyl-2-(4-(methanesulfonyl)-3-(trifluoromethyl)-phenyl)-acrylic acid (255 mg, 0.65 mmol). After 15 min at 0° C., the reaction mixture became clear. The clear solution was then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (193 mg, 1.95 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (50 mL) and a 1N aqueous hydrochloric acid solution (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30) mL). The combined organic extracts were successively washed with a 1N aqueous hydrochloric acid solution (1×50 mL), a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL). The organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 4/1 to 2/1 hexanes/ethyl acetate) afforded the pure (E)-3-cycloheptyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-acrylamide (133 mg, 43%) as an amorphous solid.

1. waitAfter 15 min at 0° C.
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 1.5 h
4. stirringthe resulting suspension was stirred for 2 d at 25° C
5. concentrationThe reaction mixture was concentrated in vacuo
6. customto remove methylene chloride
7. additionthe residue was diluted with ethyl acetate (50 mL)
8. customThe two layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate (1×30) mL)
10. washThe combined organic extracts were successively washed with a 1N aqueous hydrochloric acid solution (1×50 mL)
11. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo