반응 #1569950

반응 방정식

mono-methyl fumarate

toluene

N,N-diethylchloroacetamide

triethylamine

→

(N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate

용매

water

반응 조건

후처리

1. 1
   기타is adjusted to 85-95° C.
2. 2
   온도maintained there for 4 hours
3. 3
   기타is then adjusted to 15-25° C.
4. 4
   기타to separate for 30 minutes
5. 5
   세척The upper organic phase is washed with additional deionized water (75 mL) with vigorous agitation for 30 minutes
6. 6
   기타to separate for 30 minutes
7. 7
   건조The organic layer is dried over anhydrous sodium sulfate (25 g) for 2 hours
8. 8
   여과The reaction is filtered
9. 9
   workup.ADDITIONHeptane (1600 mL), at −5 to −20° C. is added over 5 minutes
10. 10
    온도The reaction is cooled to −5° C. to −10° C. for 24 to 48 hours
11. 11
    기타dried for 12 hours

실험 절차

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.

출처