反应详情

Dioxane (100 mL) was purged with nitrogen gas for 10 minutes. Phenanthrolene (1.0 g) and copper (I) iodide (1.0 g) were added to the dioxane, the suspension was allowed to stir under a nitrogen atmosphere for 5 minutes, and then cesium carbonate (18.72 g, 57.45 mmol), dimethyl malonate (5.46 g, 50.6 mmol), and 1-iodo-3-(trifluoromethyl)benzene (12.5 g, 46.0 mmol) were added. The reaction mixture was heated to reflux for 18 hours and then cooled to room temperature. Aqueous 1N HCl was added to the reaction mixture, the layers were separated, and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over magnesium sulfate and filtered. Celite® diatomaceous filter aid (5 g) was added to the filtrate, and the resulting suspension was concentrated under reduced pressure at 50° C. to yield a solid consisting of the crude product adsorbed onto Celite®. This solid was purified by silica gel chromatography eluting with a gradient of 100% hexanes to 25% ethyl acetate in hexanes to yield 7.36 g (58.0%) of the title product. 1H NMR (CDCl3) δ 7.59-7.65 (m, 3H), 7.49 (t, 1H), 4.70 (s, 1H), 3.76 (s, 6H).

1. customDioxane (100 mL) was purged with nitrogen gas for 10 minutes
2. additionPhenanthrolene (1.0 g) and copper (I) iodide (1.0 g) were added to the dioxane
3. temperatureThe reaction mixture was heated
4. temperatureto reflux for 18 hours
5. customthe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
7. dry with materialThe combined organic layers were dried over magnesium sulfate
8. filtrationfiltered
9. additionCelite® diatomaceous filter aid (5 g) was added to the filtrate
10. concentrationthe resulting suspension was concentrated under reduced pressure at 50° C.
11. customto yield a solid
12. customThis solid was purified by silica gel chromatography
13. washeluting with a gradient of 100% hexanes to 25% ethyl acetate in hexanes