反应详情

温度

35 °C

1108 g (2.85 mol) 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 tert-amylalcohol. During this time 3 L 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. The oily residue was combined twice with 3 L isopropyl acetate and distilled off. Then the residue was dissolved hot in 7 L isopropyl acetate and slowly cooled to RT. The precipitated solid was suction filtered, washed with 2 L isopropyl acetate and tert.-butyl-methylether and dried at 50° C.

1. distillationDuring this time 3 L 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. distillationdistilled off
10. dissolutionThen the residue was dissolved hot in 7 L isopropyl acetate
11. temperatureslowly cooled to RT
12. filtrationfiltered
13. washwashed with 2 L isopropyl acetate and tert.-butyl-methylether
14. customdried at 50° C.