反应详情

温度

-5 °C

A three neck round bottom flask equipped with a magnetic stir bar, a dropping funnel and a thermometer, was charged with CuBr (629 mg, 4.4 mmol) and HBr (25 mL). The solution was cooled to −5° C. (ice salt bath). Solid 5-morpholino-2-nitropyridin-3-amine (983 mg, 4.4 mmol) was slowly added, followed by the slow addition of a NaNO2 (333 mg, 4.8 mmol) solution in H2O (25 mL) via the dropping funnel, ensuring that the temperature did not rise above 0° C. The reaction mixture was stirred at −5° C. for 1 h, warmed to room temperature and stirred an additional 1.5 h. The reaction was deemed complete by LCMS and the mixture was cooled again to 0° C., quenched with 6 N NaOH to pH 12, diluted with water and extracted with EtOAc. EtOAc was washed with water (×2), brine (×1) dried and concentrated. The residue was azeotroped with EtOH dried under high vacuum, obtaining 4-(5-bromo-6-nitropyridin-3-yl)morpholine (1.21 g, 4.20 mmol, 96% yield) as a light yellow solid. LCMS (m/z): 288.2 (MH+), 0.65 min. 1H NMR (400 MHz, CDCl3) δ ppm 8.08-7.99 (d, J=2.3 Hz, 1H) 7.41 (d, J=2.3 Hz, 1H) 3.98-3.81 (m, 4H) 3.45-3.30 (m, 4H).

1. customA three neck round bottom flask equipped with a magnetic stir bar, a dropping funnel
2. customdid not rise above 0° C
3. temperaturewarmed to room temperature
4. stirringstirred an additional 1.5 h
5. temperaturethe mixture was cooled again to 0° C.
6. customquenched with 6 N NaOH to pH 12
7. additiondiluted with water
8. extractionextracted with EtOAc
9. washEtOAc was washed with water (×2), brine (×1)
10. customdried
11. concentrationconcentrated
12. customThe residue was azeotroped with EtOH
13. customdried under high vacuum