Reaction #161672

Reaction equation

water

benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate

sodium hydrogen carbonate

1,4-bis-(diphenylphosphino)-butane

→

benzyl 4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-piperidine-1-carboxylate

Solvents

tert-amylalcohol

Conditions

Workup

1. 1
   workup.DISTILLATION3 L of solvent were distilled off
2. 2
   workup.ADDITIONmixed with 11 mL water
3. 3
   Temperaturethe mixture was refluxed
4. 4
   Temperaturecooled to RT
5. 5
   OtherThe organic phase was separated off
6. 6
   Washwashed with 5 L water
7. 7
   Otherevaporated down
8. 8
   workup.DISTILLATIONdistilled off
9. 9
   workup.DISSOLUTIONThen the residue was dissolved hot in 7 L isopropyl acetate
10. 10
    Temperatureslowly cooled to ambient temperature
11. 11
    OtherThe solid that crystallised out
12. 12
    Filtrationfiltered
13. 13
    Washwashed with 2 L isopropyl acetate and tert.-butyl-methylether
14. 14
    Otherdried at 50° C.

Procedure

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.

Source