反応 #89454

反応方程式

product

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

CsF

2-(tributylstannyl)pyrimidine

→

title compound

収率 56.9%

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

収率 56.9%

溶媒

DMF

EtOAc

反応条件

後処理

1. 1
   その他was flushed with argon gas for 10 min
2. 2
   温度After this time, the reaction mixture was cooled to rt
3. 3
   ろ過filtered through a short pad of diatomaceous earth
4. 4
   洗浄The filter cake was rinsed with EtOAc (50 mL) and water (50 mL)
5. 5
   その他The layers of the combined filtrate were separated
6. 6
   抽出The aqueous layer was extracted with EtOAc (3×50 mL)
7. 7
   洗浄The combined organic layers were washed with 10% aq. LiCl (3×50 mL)
8. 8
   乾燥dried over Na2SO4
9. 9
   ろ過filtered
10. 10
    濃縮concentrated under reduced pressure
11. 11
    その他The residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes)

実験手順

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.

出典