反应详情

温度

40 °C

Flask A: A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, condenser, and temperature probe; the flask was charged with hydroxylamine hydrochloride (Fluka; 12.47 g, 179 mmol), Na2SO4 (51.7 g, 364 mmol), 2,2,2-trichloro-1-ethoxyethanol (15.78 g, 82 mmol), and water (240 ml). This was stirred to 40° C. to affect dissolution. Flask B: A mixture of 2-bromo-3-fluoroaniline (10.33 g, 54.4 mmol) in water (32.0 mL)/conc. HCl (14.95 mL, 179 mmol) was stirred at RT and then at 50° C. to attempt dissolution; EtOH (10 mL) was added as another attempt to dissolve the aniline to no avail. The fine slurry was added to Flask A containing the stirring 2,2,2-trichloro-1-ethoxyethanol solution at 40° C. The reaction was heated to 100° C. and was stirred for 1 h. The reaction was cooled to 5° C. in an ice bath, filtered through a disposable 0.45 micron ZapCap filter (very slow filtration), and washed with water to give N-(2-bromo-3-fluorophenyl)-2-(hydroxyimino)acetamide (12.34 g, 47.3 mmol, 87% yield) as a brown solid after it was dried in a vacuum oven. 1H NMR (400 MHz, CDCl3) δ ppm 6.92 (td, J=8.31, 1.37 Hz, 1H), 7.32 (td, J=8.31, 6.26 Hz, 1H), 7.60 (s, 1H), 7.87 (s, 1H), 8.25 (d, J=8.41 Hz, 1H), 8.98 (br. s., 1H). 19F NMR (377 MHz, CDCl3) δ ppm −104.01 (s, 1F). MS (ESI, pos. ion) m/z: 260.9/262.9 (M+1).

1. customFlask A: A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, condenser
2. dissolutiondissolution
3. customat 50° C.
4. dissolutiondissolution
5. temperatureThe reaction was heated to 100° C.
6. stirringwas stirred for 1 h
7. temperatureThe reaction was cooled to 5° C. in an ice bath
8. filtrationfiltered through a disposable 0.45 micron ZapCap
9. filtrationfilter (
10. filtrationvery slow filtration), and
11. washwashed with water