反应详情

温度

15 °C

At a temperature of about 50-70° C., under a nitrogen atmosphere, a slurry of mono-methyl fumarate (130 g), toluene (800 mL) and N,N-diethylchloroacetamide (157 g) is added to triethylamine (1.07 g). The temperature is adjusted to 85-95° C. and maintained there for 4 hours. Then the temperature is then adjusted to 15-25° C. and the mixture is subjected to vigorous agitation. After 30 minutes of vigorous agitation in 200 mL of water, the agitation is stopped and the phases are allowed to separate for 30 minutes. The upper organic phase is washed with additional deionized water (75 mL) with vigorous agitation for 30 minutes. The agitation is then stopped and the phases are allowed to separate for 30 minutes. The organic layer is dried over anhydrous sodium sulfate (25 g) for 2 hours. The reaction is filtered and the solution is cooled to 10-20° C. Heptane (1600 mL), at −5 to −20° C. is added over 5 minutes. The reaction is cooled to −5° C. to −10° C. for 24 to 48 hours. The resulting product is air dried for 12 hours. XRPD analysis confirms product is form 4.

1. customis adjusted to 85-95° C.
2. temperaturemaintained there for 4 hours
3. customis then adjusted to 15-25° C.
4. customto separate for 30 minutes
5. washThe upper organic phase is washed with additional deionized water (75 mL) with vigorous agitation for 30 minutes
6. customto separate for 30 minutes
7. dry with materialThe organic layer is dried over anhydrous sodium sulfate (25 g) for 2 hours
8. filtrationThe reaction is filtered
9. additionHeptane (1600 mL), at −5 to −20° C. is added over 5 minutes
10. temperatureThe reaction is cooled to −5° C. to −10° C. for 24 to 48 hours
11. customdried for 12 hours