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. The so obtained salt is exposed to humid atmosphere (>70% RH) at 25° C. to provide 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