Dimethylformamide → 4-Bromo-3,5-difluoro-2-((trimethylsilyl)ethynyl)aniline

A solution of 4-bromo-3,5-difluoro-2-iodoaniline (3.0 g, 9.0 mmol) in triethylamine (50 mL) was degassed with nitrogen for 10 minutes, then treated with copper iodide (209 mg, 1.10 mmol), Dichlorobis(triphenylphosphine)palladium(II), (769 mg 1.10 mmol), and ethynyl(trimethyl)silane (1.42 mL, 10.1 mmol). The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture turned dark and formed a precipitate. After two hours, the reaction mixture was treated with DMF (8 mL) and stirred for an additional 72 hours at room temperature. The reaction mixture was heated to 50° C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo, azeotroping with heptanes (3×100 mL). The black oil was partitioned between diethyl ether (300 mL) and water (300 mL), and the organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give a dark solid. The crude product was purified by flash chromatography to give the title compound (1.75 g). MS (ES+) 306.0 ((M+2)+H)+.

1. customformed a precipitate
2. waitAfter two hours
3. stirringstirred for an additional 72 hours at room temperature
4. temperatureThe reaction mixture was heated to 50° C. for 16 hours
5. temperatureAfter cooling to room temperature
6. concentrationthe reaction mixture was concentrated in vacuo
7. customazeotroping with heptanes (3×100 mL)
8. customThe black oil was partitioned between diethyl ether (300 mL) and water (300 mL)
9. washthe organic phase was washed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto give a dark solid
14. customThe crude product was purified by flash chromatography

ORD record

ord-1b3a90da500a485da0466d0f083ed226

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889730B2