反应详情

温度

35 °C

1108 g (2.85 mol) of benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate were refluxed with 720 g (8.57 mol) sodium hydrogen carbonate in 14.5 L of tert-amyl alcohol. 3 L of solvent were distilled off. The reaction mixture was cooled to 35° C. and mixed with 11 mL water. Then 13 g (0.058 mol) palladium acetate and 49 g (0.115 mol) 1,4-bis-(diphenylphosphino)-butane (DPPB) were added and the mixture was heated to reflux temperature. It was stirred at 100° C. until the reaction was complete, then cooled to RT and 7.5 L of water were added. The organic phase was separated off, washed with 5 L water and then evaporated down. Two lots of 3 L of isopropyl acetate were added to the oily residue and it was distilled off. Then the residue was dissolved hot in 7 L of isopropyl acetate and the mixture was slowly cooled to ambient temperature. The solid that crystallised out was suction filtered, washed with 2 L isopropyl acetate and tert.-butyl-methylether and dried at 50° C.

1. distillation3 L of solvent were distilled off
2. additionmixed with 11 mL water
3. temperaturethe mixture was heated
4. temperatureto reflux temperature
5. temperaturecooled to RT
6. customThe organic phase was separated off
7. washwashed with 5 L water
8. customevaporated down
9. additionTwo lots of 3 L of isopropyl acetate were added to the oily residue and it
10. distillationwas distilled off
11. dissolutionThen the residue was dissolved hot in 7 L of isopropyl acetate
12. temperaturethe mixture was slowly cooled to ambient temperature
13. customThe solid that crystallised out
14. filtrationfiltered
15. washwashed with 2 L isopropyl acetate and tert.-butyl-methylether
16. customdried at 50° C.