In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 65854-91-3 as follows. 65854-91-3
EXAMPLE 3 Preparation of 4-Chloro-2-trifluoroacetylaniline, hydrochloride hydrate. 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; 1 H NMR (300 MHz, DMSO-d6) d 7.65-7.5 (complex, 2H), 7.1 (d, J=8 Hz, 1H), 7.0 (brs, 3H); 19 F NMR (282 MHz, DMSO-d6) delta-69.5.
According to the analysis of related databases, 65854-91-3, the application of this compound in the production field has become more and more popular.
Reference:
Patent; DuPont Pharmaceuticals Company; US6028237; (2000); A;,
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