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. Then a solution of 1.25 kg (3.63 mol) benzyl 4-(2-chloro-pyridin-3-yl-amino)-piperidine-1-carboxylate in 7 L THF was added dropwise to this mixture within one hour such that the temperature of the reaction mixture did not exceed −7° C. The mixture was stirred for a further 90 minutes at approx. −8° C. and then 700 mL water was added dropwise within 30 minutes. The mixture was stirred for another 30 minutes at approx. 10° C. and then slowly combined with 8.1 L sodium hydroxide solution (2 mol/L). The reaction mixture was then heated to 50° C. and the phases were separated. The organic phase was washed with 2 L water. Then 10 L solvent were distilled off from the organic phase, 15 L butyl acetate were added to the residue and another 8 L were distilled off. By slow cooling to 0° C. the product was crystallised. 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 another 30 minutes at approx. 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 water
6. distillationThen 10 L solvent were distilled off from the organic phase, 15 L butyl acetate
7. additionwere added to the residue
8. distillationanother 8 L were distilled off
9. temperatureBy slow cooling to 0° C. the product
10. customwas crystallised
11. filtrationfiltered
12. washwashed with 2 L butyl acetate
13. customdried at 40° C.