反应详情

温度

100 °C

Under nitrogen, a mixture of tert-butyl [(1S)-2-(4-bromo-3-fluorophenoxy)-1-methylethyl]carbamate (23.3 g), ethynyl(trimethyl)silane (13.1 g), bis(triphenylphosphine)palladium(II) dichloride (4.70 g), cuprous iodide (1.27 g), triethylamine (14.0 mL), and toluene (20 mL) was stirred at 100° C. overnight. The precipitate was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in THF (200 mL), and tetrabutylammonium fluoride (1.0 M solution in THF, 201 mL) was added dropwise at room temperature. The mixture was stirred at room temperature for 2 hr. 1 M hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) and washed with hexane to give the title compound (12.2 g) as a light brown solid.

1. filtrationThe precipitate was filtered
2. concentrationthe filtrate was concentrated under reduced pressure
3. dissolutionThe residue was dissolved in THF (200 mL)
4. additiontetrabutylammonium fluoride (1.0 M solution in THF, 201 mL) was added dropwise at room temperature
5. stirringThe mixture was stirred at room temperature for 2 hr
6. addition1 M hydrochloric acid was added
7. extractionthe mixture was extracted with ethyl acetate
8. washThe organic layer was washed with brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
12. washwashed with hexane