反应详情

315 g of oxalyl chloride (2.48 mol) were added at a temperature between 15 and 18° C. over 24 min to a mixture of 650 g of 2-((E)-2-ethoxycarbonylvinyl)-4-trifluoromethylbenzoic acid (2.25 mol), 33 ml of DMF and 7.8 l of CH2Cl2. During the addition, gas evolution was observed. The mixture was stirred at RT for 1 h and then cooled to 5° C., and 285 g of Et3N (2.81 mol) was then added at a temperature between 5° C. and 10° C. over a period of 27 min. The mixture was stirred at 5° C. for a further 10 min, then 279 g of 2,2,2-trifluoroethylamine (2.81 mol) were added at a temperature between 9° C. and 20° C. over a period of 27 min. The mixture was stirred at RT for 10 min, in the course of which a thick precipitate precipitated out, and, to improve the stirrability of the mixture, an additional 1 l of CH2Cl2 was added. The reaction was monitored by HPLC (method C; 2-((E)-2-ethoxycarbonylvinyl)-4-trifluoromethylbenzoic acid rt=5.9 min; ethyl (E)-3-[2-(2,2,2-trifluoroethylcarbamoyl)-5-trifluoromethylphenyl]acrylate rt=13.2 min). After stirring at RT for a further 50 min, the reaction was complete. Volatile constituents of the reaction mixture were then removed under reduced pressure, and the residue was taken up with 12 l of EA and washed 3 times with 2.5 l each time of water, then twice with 2.5 l each time of a saturated aqueous NaHCO3 solution and finally with 1.5 l of a saturated aqueous NaCl solution. Drying was effected over MgSO4, and the solvent was removed under reduced pressure to obtain 802 g of ethyl (E)-3-[2-(2,2,2-trifluoroethylcarbamoyl)-5-trifluoromethylphenyl]acrylate as a brown solid. This crude substance was combined with the crude product of another batch (177 g) and dissolved at 60-70° C. in 3 l of EA, and 14 l of HEP were added at this temperature in 1 l portions. The mixture was then heated to 80° C. and stirred at this temperature for 1.5 h. This mixture was then added to 5.6 l of HEP at 70° C. and the mixture was then cooled to RT with stirring over a period of 5 h. The product was then filtered off, washed with 3 l of HEP and dried under air to obtain 689 g of ethyl (E)-3-[2-(2,2,2-trifluoroethylcarbamoyl)-5-trifluoromethylphenyl]acrylate (67%) as a light brown solid. Mp: 161.5-162° C.

1. additionDuring the addition, gas evolution
2. temperaturecooled to 5° C.
3. stirringThe mixture was stirred at 5° C. for a further 10 min
4. stirringThe mixture was stirred at RT for 10 min, in the course of which a thick precipitate
5. customprecipitated out
6. additionan additional 1 l of CH2Cl2 was added
7. customwas monitored by HPLC (method C; 2-((E)-2-ethoxycarbonylvinyl)-4-trifluoromethylbenzoic acid rt=5.9 min; ethyl (E)-3-[2-(2,2,2-trifluoroethylcarbamoyl)-5-trifluoromethylphenyl]acrylate rt=13.2 min)
8. stirringAfter stirring at RT for a further 50 min
9. customVolatile constituents of the reaction mixture were then removed under reduced pressure
10. washwashed 3 times with 2.5 l each time of water
11. customDrying
12. customthe solvent was removed under reduced pressure