反应详情

温度

-20 °C

N-(4-Chlorophenyl)-2,2-dimethyl propanamide (36.7 kg, 173 mol) was charged to a solution of TMEDA (20.2 kg, 174 mol) in anhydrous t-butyl methyl ether (271.5 kg) and cooled to -20° C. To the cold slurry was added 2.7 N n-butyllithium in hexane (101.9 kg, 393 mol) while keeping the temperature below 5° C. After aging 2 hr at 0 to 5° C., the solution was cooled below -15° C. then rapidly reacted with ethyl trifluoroacetate (34.5 kg, 243 mol). After 30 min, the resulting solution was quenched into 3N HCl (196 L, 589 mol) keeping the temperature below 25° C. After removal of the aqueous phase, the organic solution was concentrated by distilling approximately 200 L of solvent. Acetic acid (352 kg) was added while distilling 325 kg solvent under 100 mm vacuum. After cooling the solution to 30° C., 12 N HCl (43.4 kg, 434 mol) was added and the mixture heated to 65 to 70° C. and held 4 hours. The resulting slurry was cooled to 5° C. and the product was collected by filtration, washed with ethyl acetate (50.5 kg) and dried in vacuo to give 42.1 kg (87%) of the title compound as a white crystalline solid: mp 159-162 dec; 1H NMR (300 MHz, DMSO-d6) d 7.65-7.5 (complex, 2H), 7.1 (d, J=8 Hz, 1H), 7.0 (brs, 3H); 19F NMR (282 MHz, DMSO-d6) δ -69.5.

1. customthe temperature below 5° C
2. temperaturethe solution was cooled below -15° C.
3. waitAfter 30 min
4. customthe temperature below 25° C
5. customAfter removal of the aqueous phase
6. concentrationthe organic solution was concentrated
7. distillationby distilling approximately 200 L of solvent
8. additionAcetic acid (352 kg) was added
9. distillationwhile distilling 325 kg solvent under 100 mm vacuum
10. temperatureAfter cooling the solution to 30° C.
11. temperaturethe mixture heated to 65 to 70° C.
12. waitheld 4 hours
13. temperatureThe resulting slurry was cooled to 5° C.
14. filtrationthe product was collected by filtration
15. washwashed with ethyl acetate (50.5 kg)
16. customdried in vacuo