Реакция #89454

Уравнение реакции

product

2-(((2S,3R)-1-(5-Fluoro-2-iodobenzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

CsF

2-(tributylstannyl)pyrimidine

→

title compound

Выход 56.9%

2-(((2S,3R)-1-(5-fluoro-2-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

Выход 56.9%

Растворители

DMF

EtOAc

Условия реакции

Обработка

1. 1
   Другоеwas flushed with argon gas for 10 min
2. 2
   ТемператураAfter this time, the reaction mixture was cooled to rt
3. 3
   Фильтрацияfiltered through a short pad of diatomaceous earth
4. 4
   ПромывкаThe filter cake was rinsed with EtOAc (50 mL) and water (50 mL)
5. 5
   ДругоеThe layers of the combined filtrate were separated
6. 6
   ЭкстракцияThe aqueous layer was extracted with EtOAc (3×50 mL)
7. 7
   ПромывкаThe combined organic layers were washed with 10% aq. LiCl (3×50 mL)
8. 8
   Сушкаdried over Na2SO4
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеconcentrated under reduced pressure
11. 11
    ДругоеThe residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes)

Методика

A suspension of the product of Step 228a (537 mg, 1.05 mmol), CsF (322 mg, 2.13 mmol), and CuI (40 mg, 0.210 mmol) in anhydrous DMF (5 mL) was flushed with argon gas for 10 min, then 2-(tributylstannyl)pyrimidine (582 mg, 1.58 mmol) and Pd(PPh3)4 (122 mg, 0.105 mmol) were added at rt. The reaction mixture was then heated to 105° C. under nitrogen for 16 h. After this time, the reaction mixture was cooled to rt, diluted with EtOAc (100 mL), and filtered through a short pad of diatomaceous earth. The filter cake was rinsed with EtOAc (50 mL) and water (50 mL). The layers of the combined filtrate were separated. The aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with 10% aq. LiCl (3×50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes) to afford the title compound as a yellow foam (274 mg, 56%): ESI MS (M+H) 459.

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