反应详情

温度

-2 °C

To a suspension of 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea (21.36 kg) in CH3OH (178 L) is added aqueous H2SO4 (6 L, 9.91%) during 10 min. The clear solution is filtered and further aqueous H2SO4 (33.8 L, 1.07 M) is added during 45 min. The solution is cooled to −2° C. during 1.5 h and stirred at −5 to −9° C. for 1 h. The formed precipitate is filtered, washed with cooled CH3OH (−5° C., 54 L) and dried under a stream of nitrogen provide 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea of formula I sulfate as a non-defined hydrate. A slurry of the so obtained salt in H2O (16.2% w/w) is stirred for 3 days at 25° C. Filtration and drying at 30° C. under a wet stream of nitrogen (50% RH) provides the title compound.

1. filtrationThe clear solution is filtered
2. additionfurther aqueous H2SO4 (33.8 L, 1.07 M) is added during 45 min
3. filtrationThe formed precipitate is filtered
4. washwashed with cooled CH3OH (−5° C., 54 L)
5. customdried under a stream of nitrogen