Application of 654-70-6, A common heterocyclic compound, 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, molecular formula is C8H5F3N2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Thionyl chloride (2.4 ml, 33.6 mmol) was added dropwise to (R)-3-bromo-2-hydroxy-2-methylpropionic acid (5.11).Gram, 28 mmol) in a solution of 30 ml of THF,The temperature of the drop is controlled at 0-12 C.It takes 10 minutes.The resulting mixture was stirred under the same conditions for 2 hours.The internal temperature was adjusted to about -5 C, and triethylamine (Et3N) (5.0 ml, 36.4 mmol, 1.3 eq) was slowly added to the reaction mixture, and the internal temperature was lower than 12 C during the addition.Stir for 20 minutes under the same reaction conditions.Then, a solution of 4-cyano-3-trifluoromethyl-phenylamine (4.0 g, 21 mmol) in 40 mL of THF was added dropwise, and the mixture was stirred at 50 C for two hours.The reaction solution was cooled to 20 ± 5 C, then water (15 ml, 2.9 vol) and toluene (20 ml, 4.0 vol) was added, and after stirring, the mixture was separated and the organic phase was washed with water (15 ml, 2.9 vol.). After the combination, it was concentrated to 5 ± 0.5 volume (6.4% by weight) by distillation under reduced pressure, and the temperature was kept below 50 C during the distillation. Add toluene (31 ml, 6 volumes) to the concentrate, dilute to 5 ± 0.5 volume (6.4 wt), adjust the temperature to 2.5 ± 2.5 C, stir at this temperature for one hour, add seed crystal (0.018 g, 0.005 wt) Stirring was continued for one hour, filtered, and the filter cake was washed twice with toluene (8.5 ml each time, 1.7 volumes each time). The batch is then dried in a vacuum oven.Get 5.8 grams(R)-3-Bromo-N-(4-cyano-3-trifluoromethyl-phenyl)-2-hydroxy-2-methylpropanamide.Yield 59%, HPLC (mobile phase is water and acetonitrile) purity 99% (220 nm), 99% (254 nm), optical HPLC purity 99%.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; Yang Guohong; He Junze; Duan Meijuan; (34 pag.)CN108558760; (2018); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts