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. 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 refluxed. It was stirred at 100° C. until the reaction was complete, cooled to RT and 7.5 L water were added. The organic phase was separated off, washed with 5 L water and then evaporated down. The oily residue was twice combined with 3 L isopropyl acetate and distilled off. Then the residue was dissolved hot in 7 L isopropyl acetate and 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 refluxed
4. temperaturecooled to RT
5. customThe organic phase was separated off
6. washwashed with 5 L water
7. customevaporated down
8. distillationdistilled off
9. dissolutionThen the residue was dissolved hot in 7 L isopropyl acetate
10. temperatureslowly cooled to ambient temperature
11. customThe solid that crystallised out
12. filtrationfiltered
13. washwashed with 2 L isopropyl acetate and tert.-butyl-methylether
14. customdried at 50° C.