反应详情

温度

62.5 °C

A 250 mL reactor under N2 is successively loaded with 91 (5 g, 19.41 mmol), dichloroethane (50 mL), DMF (0.014 mL, 1% mol) and oxalyl chloride (1.86 mL, 21.35 mmol). The mixture is heated up to 60-65° C. for 2 h, before being cooled to 0° C. Then, morpholine (6.93 g, 79.60 mmol) in dichloroethane (20 mL) is added over 15 min keeping the temperature below 10° C. The heterogeneous solution is post-agitated for 1 h 30 min at room temperature and quenched with water (30 mL). The biphasic mixture is filtered on a Hyflo Super Cel® (10 g), then after separation, the organic layer is concentrated under reduce pressure. The mixture is taken up with isopropanol (80 mL) and 12N HClaq (1.61 mL, 19.41 mmol), stirred for 10 min and concentrated under reduce pressure. The mixture is taken up with isopropanol (13 mL), heated to reflux until a homogeneous solution is formed, then it is cooled to room temperature. The precipitate is filtered, rinsed with isopropanol (10 mL) and dried under vacuum at 40° C. overnight to obtain 92 as an off-white powder with 79% overall yield.

1. temperaturebefore being cooled to 0° C
2. customthe temperature below 10° C
3. customquenched with water (30 mL)
4. filtrationThe biphasic mixture is filtered on a Hyflo Super Cel® (10 g)
5. customafter separation
6. concentrationthe organic layer is concentrated
7. stirringstirred for 10 min
8. concentrationconcentrated
9. temperatureheated
10. temperatureto reflux until a homogeneous solution
11. customis formed
12. temperatureit is cooled to room temperature
13. filtrationThe precipitate is filtered
14. washrinsed with isopropanol (10 mL)
15. customdried under vacuum at 40° C. overnight