反应详情

温度

0 °C

Sodium hydrogen carbonate (26.0 kg, 1.7 mol eq) was charged followed by acetone (58.6 L, 2 rel vol). 3-(Trifluoromethyl)aniline (29.3 kg, 1 mol eq, limiting reagent) was charged followed by addition of acetone (14.7 L, 0.5 rel vol) and the mixture cooled to 0° C. Methyl malonyl chloride (25.8 kg, 1.05 mol eq) was diluted with acetone (29.3 L, 1 rel vol) and charged maintaining the temperature below 20° C. An acetone line rinse (14.7 L, 0.5 rel vol) was charged and the reaction mixture was stirred until HPLC confirmed the reaction to be complete. Water (293 L, 10 rel vol) was then charged and acetone was removed by distillation. The reaction was then cooled to 20° C. A further portion of water was added (171.2 L, 4 rel vol) and the reaction was stirred to precipitate out the product. The solid was isolated by filtration, washed twice with water (2×58.6 L, 2×2 rel vol), once with iso-hexane (146.5 L, 5 rel vol) and dried to constant weight to yield the title compound (39.5 kg, 151.7 mol, 84%); 1H NMR (CDCl3): δ 3.51 (s, 2H); 3.82 (s, 3H); 7.38 (d, 1H, J=7.9 Hz); 7.45 (t, 1H, J=7.9 Hz); 7.76 (d, 1H, J=7.7 Hz); 7.85 (s, 1H); 9.42 (s, 1H) ppm; LCMS: m/z 262.2 (MH+).

1. additionwas charged
2. additioncharged
3. temperaturemaintaining the temperature below 20° C
4. washAn acetone line rinse (14.7 L, 0.5 rel vol)
5. additionwas charged
6. customthe reaction
7. customacetone was removed by distillation
8. temperatureThe reaction was then cooled to 20° C
9. additionA further portion of water was added (171.2 L, 4 rel vol)
10. stirringthe reaction was stirred
11. customto precipitate out the product
12. customThe solid was isolated by filtration
13. washwashed twice with water (2×58.6 L, 2×2 rel vol), once with iso-hexane (146.5 L, 5 rel vol)
14. customdried to constant weight