Реакция #157828

Уравнение реакции

water

(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(tributylstannyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

cesium fluoride

6-iodo-2-methoxypyridin-3-amine

→

(5R)-5-[(E)-2-(5-amino-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

Растворители

ethyl acetate

N,N-dimethylformamide

Условия реакции

Обработка

1. 1
   workup.WAITThe reaction solution was left
2. 2
   Температураto cool
3. 3
   Фильтрацияfollowed by filtration through celite
4. 4
   ЭкстракцияThe filtrate was extracted with ethyl acetate
5. 5
   ПромывкаThe organic layer was washed with water and brine
6. 6
   Сушкаdried over anhydrous magnesium sulfate
7. 7
   Другоеafter which the solvent was evaporated under reduced pressure
8. 8
   ДругоеThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:4)

Методика

Tetrakis(triphenylphosphine)palladium(0) (50 mg) was added to a solution of (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(tributylstannyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one obtained in Reference Example 4-26 (296 mg), 6-iodo-2-methoxypyridin-3-amine obtained in Reference Example 4-31(1) (220 mg), cesium fluoride (135 mg) and copper iodide (93 mg) in N,N-dimethylformamide (1.5 mL) in a nitrogen atmosphere, and the mixture was stirred at 65° C. for three hours. The reaction solution was left to cool, and then water and ethyl acetate were added, followed by filtration through celite. The filtrate was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:4) to give (5R)-5-[(E)-2-(5-amino-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a light brown amorphous (152 mg, 68%).

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