反应详情

Benzoic acid (1451 g, 11.9 mol) and MTBE (5.8 L) were added to a 50 L 3-necked round-bottom flask equipped with a mechanical stirrer, thermometer, nitrogen inlet and heating mantle. The resulting slurry was heated at 45° C. to 50° C. to dissolve the benzoic acid. A solution of 4-isopropylamino-1-(4-methoxypyrid-3-ylmethyl)piperidine (3130 g, 11.9 mol) in methy tert-butyl ether (MTBE) (13.7 L) was added at 45° C. to 50° C. and the resulting mixture was stirred at reflux (50° C. to 55° C.) for 30 minutes and then at ambient temperature for 16 hours. The reaction mixture was then cooled to 0° C. to 5° C. with an ice/methanol bath and stirred for 30 minutes at which time a solid had formed. The solid was filtered through a polypropylene filter pad and washed with MTBE (3×2 L) and ethyl ether (3×2 L). The solid was then tray dried in a vacuum oven at room temperature until a constant weight was obtained to provide the title compound (3805 g, 82% yield).

1. customequipped with a mechanical stirrer
2. temperaturethermometer, nitrogen inlet and heating mantle
3. temperatureThe resulting slurry was heated at 45° C. to 50° C.
4. temperatureat reflux (50° C. to 55° C.) for 30 minutes
5. temperatureThe reaction mixture was then cooled to 0° C. to 5° C. with an ice/methanol bath
6. stirringstirred for 30 minutes at which time a solid
7. customhad formed
8. filtrationThe solid was filtered through a polypropylene
9. filtrationfilter pad
10. washwashed with MTBE (3×2 L) and ethyl ether (3×2 L)
11. customtray dried in a vacuum oven at room temperature until a constant weight
12. customwas obtained