Реакция #160686

Уравнение реакции

potassium hydrogen carbonate

(2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide

triethylamine

di-t-butyldicarbonate

Methanesulfonic acid

carbonyl diimidazole

→

(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide

Растворители

toluene

toluene

toluene

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas added to the reaction mixture
2. 2
   workup.ADDITIONwas added
3. 3
   Другоеto 20° C.
4. 4
   workup.STIRRINGthe mixture was stirred at 20° C. until the reaction
5. 5
   ДругоеThe aqueous layer was separated
6. 6
   Промывкаthe toluene layer washed with water (3 mL), citric acid (1N, 3 mL) and water (3 mL)
7. 7
   ЭкстракцияThe four aqueous washes were twice back-extracted with dichloromethane (2×3 mL)

Методика

(2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide (291 mg, 1.17 mmol) was mixed with triethylamine (193 □l, 1.37 mmol) and toluene (2.4 ml) at 20° C. di-t-butyldicarbonate (310 mg, 1.42 mmol) as a solution in toluene (2.0 ml) was added to the reaction mixture, and the mixture was stirred at 40° C. until the reaction was complete. The solution was diluted with toluene (3.9 mL) and carbonyl diimidazole (462 mg, 2.85 mmol) was added and agitation was continued until the reaction was deemed to be complete. Methanesulfonic acid (663 □l, 10.2 mmol) was added and agitation was continued until the reaction was deemed to be complete. After lowering the temperature to 20° C., aqueous potassium hydrogen carbonate (10.2 ml, 1N, 10.2 mmol) was added and the mixture was stirred at 20° C. until the reaction was complete. The aqueous layer was separated and the toluene layer washed with water (3 mL), citric acid (1N, 3 mL) and water (3 mL). The four aqueous washes were twice back-extracted with dichloromethane (2×3 mL). The three organic extracts were combined to give (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide as a solution in toluene and dichloromethane (176 mg, 0.64 mmol, 55%).

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