反应详情

A 200 mL round-bottom flask containing a stir bar was charged with 6-bromo-2-(trans-4-tert-butylcyclohexyloxy)-1-(trifluoromethyl)naphthalene (5.00 g, 11.6 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.400 g, 0.437 mmol; Strem), 2-(di-t-butylphosphino)-2′-methylbiphenyl (0.546 g, 1.75 mmol; Strem), and cesium carbonate (4.55 g, 14.0 mmol; Alfa Aesar). The reaction vessel was capped with a rubber septum, evacuated, backfilled with argon three times and 1,2-dimethoxyethane (100 mL, 1000 mmol) and 4-nitro-butyric acid methyl ester (3.02 mL, 24.4 mmol) were added via syringe under argon. After the mixture was stirred vigorously for 2 min at room temperature, the flask was equipped with a condensor and heated at 50° C. overnight. The reaction was allowed to cool to ambient temperature and quenched with a solution of sat. aqueous ammonium chloride. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with water then dried with magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was dissolved in methylene chloride and absorbed onto silica gel, then purified by flash column chromatography (0-20% hexanes in ethylacetate) to give 2.34 g of the title compound in 41% yield.

1. additionA 200 mL round-bottom flask containing a stir bar
2. customThe reaction vessel was capped with a rubber septum
3. customevacuated
4. additionwere added via syringe under argon
5. customthe flask was equipped with a condensor
6. temperatureheated at 50° C. overnight
7. temperatureto cool to ambient temperature
8. customquenched with a solution of sat. aqueous ammonium chloride
9. customThe layers were separated
10. extractionthe aqueous phase was extracted with ethyl acetate
11. washThe combined organic phase was washed with water
12. dry with materialthen dried with magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. dissolutionThe crude product was dissolved in methylene chloride
16. customabsorbed onto silica gel
17. custompurified by flash column chromatography (0-20% hexanes in ethylacetate)