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

HRID 2059968Notes

Reaction equation

HRID 2059968 reaction equation
Cl[C:2]1[C:7]([N:8]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:14][CH2:13]2)[C:9]([NH2:11])=[O:10])=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])O.[Na+].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C(O)(CC)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:10]=[C:9]1[NH:11][C:2]2=[N:3][CH:4]=[CH:5][CH:6]=[C:7]2[N:8]1[CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 962WaterHCID 821241,4-Bis(diphenylphosphino)butaneHCID 516892Sodium BicarbonateHCID 46853854Benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate

Product 1

HCID 46853855Benzyl 4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
35 °C

Procedure

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.

Workup

  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.

Sources & evidence

ORD record
ord-76842bc13f1e43a0a7138654bec9c678
Source dataset
uspto-grants-2012_10
Patent number
US08278336B2

Reaction notes

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