반응 #89454

반응 방정식

product

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

CsF

2-(tributylstannyl)pyrimidine

→

title compound

수율 56.9%

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

수율 56.9%

용매

DMF

EtOAc

반응 조건

후처리

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

실험 절차

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.

출처