Water → Benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate

HRID 469284Notes

Reaction equation

HRID 469284 reaction equation
ClS([N:5]=[C:6]=[O:7])(=O)=O.[Cl:8][C:9]1[C:14]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[CH2:18][CH2:17]2)=[CH:13][CH:12]=[CH:11][N:10]=1.O.[OH-].[Na+]>C1COCC1>[Cl:8][C:9]1[C:14]([N:15]([CH:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:23])[CH2:20][CH2:21]2)[C:6]([NH2:5])=[O:7])=[CH:13][CH:12]=[CH:11][N:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 70918Chlorosulfonyl isocyanateHCID 46853853Benzyl 4-(2-chloro-pyridin-3-yl-amino)-piperidine-1-carboxylate

Product 1

HCID 46853854Benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

530 mL (6.1 mol) chlorosulphonyl isocyanate were placed in 6 L THF and cooled to −15° C. A solution of 1.25 kg (3.63 mol) benzyl 4-(2-chloro-pyridin-3-yl-amino)-piperidine-1-carboxylate in 7 L THF was then added dropwise to this mixture within one hour such that the temperature of the reaction mixture did not exceed −7° C. The mixture was stirred for 90 minutes at approx. −8° C. and then 700 mL water were added dropwise within 30 minutes. The mixture was stirred for 30 minutes at approx. 10° C. and then slowly combined with 8.1 L sodium hydroxide solution (2 mol/L). The reaction mixture was then heated to 50° C. and the phases were separated. The organic phase was washed with 2 L water. Then 10 L solvent were distilled off from the organic phase, 15 L butyl acetate were added to the residue and another 8 L were distilled off. The product was crystallised by slow cooling to 0° C. The precipitate was suction filtered, washed with 2 L butyl acetate and dried at 40° C.

Workup

  1. customdid not exceed −7° C
  2. stirringThe mixture was stirred for 30 minutes at approx. 10° C.
  3. temperatureThe reaction mixture was then heated to 50° C.
  4. customthe phases were separated
  5. washThe organic phase was washed with 2 L water
  6. distillationThen 10 L solvent were distilled off from the organic phase, 15 L butyl acetate
  7. additionwere added to the residue
  8. distillationanother 8 L were distilled off
  9. customThe product was crystallised
  10. temperatureby slow cooling to 0° C
  11. filtrationfiltered
  12. washwashed with 2 L butyl acetate
  13. customdried at 40° C.

Sources & evidence

ORD record
ord-72b03191f0a14a9bbdc621880319e466
Source dataset
uspto-grants-2014_01
Patent number
US08629137B2

Reaction notes

Loading…