Reaktion #72114

Reaktionsgleichung

hydrochloric acid 1,4-dioxane

tert-butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidine-1-carboxylate

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidine-1-carboxylate

Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate

sodium carbonate

→

title compound

Ausbeute 56.3%

Ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylate

Ausbeute 56.3%

Lösungsmittel

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling
2. 2
   EinengenThe reaction solution was concentrated under reduced pressure, and DMF (4 mL)
3. 3
   workup.ADDITIONwas added
4. 4
   workup.STIRRINGthe mixture was stirred at 90° C. for three hours
5. 5
   Extraktionfollowed by extraction with ethyl acetate
6. 6
   WaschenThe resulting organic layer was washed with water and brine
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   Sonstigethe insoluble matter was separated by filtration
9. 9
   EinengenThe filtrate was concentrated under reduced pressure
10. 10
    Sonstigethe resulting residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=1:1 v/v)

Vorschrift

A 4 N hydrochloric acid/1,4-dioxane solution (3 mL) was added to tert-butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidine-1-carboxylate obtained in Example (196b) (159 mg, 0.424 mmol) under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure, and DMF (4 mL) was added. Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate (117 mg, 0.467 mmol) and sodium carbonate (225 mg, 2.12 mmol) were added, and the mixture was stirred at 90° C. for three hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=1:1 v/v) to obtain 106 mg of the title compound (56%) as a colorless solid.

Quelle