Реакция #542100

Уравнение реакции

2-(4-((3-bromopyridin-2-yl)oxy)piperidin-1-yl)quinoline

piperidine-4-carbonitrile

2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

sodium tert-butoxide

→

title product

Выход 70.0%

1-(2-((1-(Quinolin-2-yl)Piperidin-4-yl)Oxy)Pyridin-3-yl)Piperidine-4-Carbonitrile

Выход 70.0%

Растворители

toluene

Условия реакции

Обработка

1. 1
   Температураheated
2. 2
   Температураat reflux overnight under N2 atmosphere
3. 3
   ФильтрацияThen the reaction mixture was filtered
4. 4
   workup.ADDITIONdiluted with water (50 mL)
5. 5
   Экстракцияextracted with EtOAc (3×20 mL)
6. 6
   ПромывкаThe combined organic extracts were washed with water (60 mL) and brine (60 mL)
7. 7
   Сушкаdried over Na2SO4
8. 8
   Фильтрацияfiltered
9. 9
   ДругоеThe filtrate was evaporated in vacuo
10. 10
    Другоеthe residue was purified by flash column chromatography on silica gel (20% to 50% EtOAc in hexanes)

Методика

To a solution of 2-(4-((3-bromopyridin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P2.2; 383 mg, 1.0 mmol) in toluene (10 mL) were added piperidine-4-carbonitrile (110 mg, 1.0 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (62 mg, 0.1 mmol) and sodium tert-butoxide (t-BuONa) (180 mg, 2.0 mmol). The mixture was stirred and heated at reflux overnight under N2 atmosphere. Then the reaction mixture was filtered, diluted with water (50 mL), and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with water (60 mL) and brine (60 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 50% EtOAc in hexanes) to give the title product (290 mg, 0.7 mmol, 70% yield) as white solid. ESI-MS (M+1): 414 calc. for C25H27BrN5O 413.

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