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

HRID 74489Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 74489
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

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

530 mL (6.1 mol) chlorosulphonyl isocyanate were placed in 6 L THF and cooled to −15° C. Then 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 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 a further 90 minutes at approx. −8° C. and then 700 mL water was added dropwise within 30 minutes. The mixture was stirred for another 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. By slow cooling to 0° C. the product was crystallised. The precipitate was suction filtered, washed with 2 L butyl acetate and dried at 40° C.

Aufarbeitung

  1. customdid not exceed −7° C
  2. stirringThe mixture was stirred for another 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. temperatureBy slow cooling to 0° C. the product
  10. customwas crystallised
  11. filtrationfiltered
  12. washwashed with 2 L butyl acetate
  13. customdried at 40° C.

Quellen und Nachweise

ORD-Eintrag
ord-53d1921418654dc1aaafc8fbcc4fb62b
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829006B2

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