反应详情

温度

-15 °C

530 mL (6.1 mol) chlorosulphonyl isocyanate were placed in 6 L THF and cooled to −15° C. A solution of 1.25 kg (3.63 mol) benzyl 4-(2-chloro-pyridin-3-yl-amino)-piperidine-1-carboxylate in 7 L of THF was then added to this mixture within one hour in such a way that the temperature of the reaction mixture did not exceed −7° C. The mixture was stirred for 90 minutes at about −8° C. and then 700 mL of water were added dropwise within 30 minutes. The mixture was stirred for 30 minutes at about 10° C. and then 8.1 L sodium hydroxide solution (2 mol/L) were slowly added. The reaction mixture was then heated to 50° C. and the phases were separated. The organic phase was washed with 2 L of water. Then 10 L of solvent were distilled off from the organic phase, 15 L of butyl acetate were added to the residue and from this another 8 L were distilled off again. The product was crystallised by slow cooling to 0° C. The precipitate was suction filtered, washed with 2 L butyl acetate and dried at 40° C.

1. customdid not exceed −7° C
2. stirringThe mixture was stirred for 30 minutes at about 10° C.
3. temperatureThe reaction mixture was then heated to 50° C.
4. customthe phases were separated
5. washThe organic phase was washed with 2 L of water
6. distillationThen 10 L of solvent were distilled off from the organic phase, 15 L of butyl acetate
7. additionwere added to the residue
8. distillationfrom this another 8 L were distilled off again
9. customThe product was crystallised
10. temperatureby slow cooling to 0° C
11. filtrationfiltered
12. washwashed with 2 L butyl acetate
13. customdried at 40° C.