反应详情

温度

47.29999923706055 °C

A 250 L reactor was charged with 10.22 kg of purified (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride, 113.0 kg of Methanol was added and the reaction mixture was heated to 47.3° C. with stirring at 120 rpm. A resulting clear brown solution was filtered warm through a GAF filter into a 200 L drum and the filter was flushed with 8.0 kg of Methanol. The reactor was cleaned with 45.0 kg of Methanol, the filtered Methanol solution was transferred from the 200 L drum into the 250 L reactor and the solution was heated to 46.3° C. with stirring at 120 rpm. At this temperature 23.5 kg of water was added during 10 min, the solution was heated to 64.3° C. during 60 min (reflux) and 26.1 kg of a solution of 1.2 kg sodium hydroxide in 30.6 kg water was added at 64.5-65.3° C. during 90 min (reflux; exotherm). The resulting beige suspension was stirred at 65.2-66.9° C. during 45 min, cooled 58-60° C. and sampled for pH-control (pH 11). The suspension was cooled to 24.8° C. during 1 h 55 min, stirred at this temperature during 13 h. The suspension was transferred into the centrifuge (filter cloth type: Lanz Anliker PP20) and centrifuged in one portion. The 250 L reactor was charged with 20.0 kg water and 16.0 kg of Methanol and stirred at 23.0° C. during 10 min. The filter cake was washed with the methanol mixture, the wet product (8.84 kg) was transferred to the tray dryer and dried at 52.2° C. and 290-1 mbar during 68 h 44 min to give 8.45 kg of (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione.

1. additionwas added
2. filtrationA resulting clear brown solution was filtered
3. temperaturewarm through a GAF
4. filtrationfilter into a 200 L drum
5. customthe filter was flushed with 8.0 kg of Methanol
6. temperaturethe solution was heated to 46.3° C.
7. stirringwith stirring at 120 rpm
8. additionAt this temperature 23.5 kg of water was added during 10 min
9. temperaturethe solution was heated to 64.3° C. during 60 min
10. temperature(reflux) and 26.1 kg of a solution of 1.2 kg sodium hydroxide in 30.6 kg water
11. additionwas added at 64.5-65.3° C. during 90 min
12. temperature(reflux; exotherm)
13. stirringThe resulting beige suspension was stirred at 65.2-66.9° C. during 45 min
14. temperaturecooled 58-60° C.
15. aliquotsampled for pH-control (pH 11)
16. temperatureThe suspension was cooled to 24.8° C. during 1 h 55 min
17. stirringstirred at this temperature during 13 h
18. filtrationThe suspension was transferred into the centrifuge (filter cloth type: Lanz Anliker PP20)
19. additionThe 250 L reactor was charged with 20.0 kg water and 16.0 kg of Methanol
20. stirringstirred at 23.0° C. during 10 min
21. washThe filter cake was washed with the methanol mixture
22. customdried at 52.2° C.