反应详情

温度

0 °C

In a 1 L 3 neck round bottom flask with a mechanical stirrer, thermocouple and nitrogen inlet charge ethanol (339.2 mL) and cool to −5 to 5° C. Add drop-wise neat acetyl chloride (78.5 g, 1 mol, 5 eq) at a rate to maintain temperature at 0-15° C. Cool the resulting solution to 0-5° C. and stir for 30 minutes. Add 4-(1-(2-(dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester (96.9 g, 0.2 mol, 1 eq) over 5-10 minutes. Warm the reaction solution to RT (crystallization takes place) and stir the resulting suspension for 20-28 hours at RT. Once the reaction is deemed complete, filter the reaction mixture and wash the solids with ethanol (3×58 mL) then with heptane (2×96.9 mL). Dry solids under vacuum at 35-40° C. to afford the target compound (105.13 g, >100% yield) as a light tan solid. m/z (M+H): 385.2

1. temperatureto maintain temperature at 0-15° C
2. temperatureCool the resulting solution to 0-5° C.
3. temperatureWarm the reaction solution to RT
4. custom(crystallization takes place)
5. stirringstir the resulting suspension for 20-28 hours at RT
6. filtrationfilter the reaction mixture
7. washwash the solids with ethanol (3×58 mL)
8. customDry solids under vacuum at 35-40° C.