Synthetic Route of 54962-75-3,Some common heterocyclic compound, 54962-75-3, name is 3-Bromo-5-(trifluoromethyl)aniline, molecular formula is C7H5BrF3N, 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.
Example 1; Preparation of 3-(trifluoromethyl)-5-(4-methyl-1H-imidazole-1-yl)-benzeneamine of formula I2000 g of 3-bromo-5-trifluoromethylaniline of formula II, 1368 g of 4-methylimidazole of formula III, 181 g of 8-hydroxyquinoline, 238 g of CuI, 666.6 g of NaOH, 933 g of CaO and 7000 ml of DMSO were loaded into a 10 L of 3-neck flask. The reaction mixture was protected with nitrogen and was then stirred at 120 C. for 69 hours while monitoring for the consumption of 3-bromo-5-trifluoromethyaniline by HPLC. Heating was stopped when 3-bromo-5- trifluoromethyaniline/4-methylimidazole is not more than 5%. The reaction mixture was cooled down to 45-50 C. and poured into a 50 L reactor. 8.4 L of 14% ammonia was added dropwise and then stirred for 1 hour at 45-50 C. The mixture was cooled down to room temperature. 16.8 L of water and 10 L of ethyl acetate were added to the extract. The upper organic layer was separated and filtered through the filter aid. The lower aqueous layer was washed with 7.5L of ethyl acetate and combined with the above filtrate. The combined organic layer was washed with 5 L¡Á3 of 5% of brine for three times. The upper organic layer was separated and dried over 1 kg of anhydrous Na2SO4 overnight. The mixture was filtered and concentrated to obtain 2.3 kg of solid. The residue was dissolved in 2 L of ethyl acetate at 45 C. To the solution was then added 8 L of petroleum ether dropwise at 45 C. The mixture was cooled down slowly to 0-15 C. and stirred for 1 hour. A large amount of precipitate was formed and filtered. The filtered cake was dissolved in 2 L of ethyl acetate at 45 C. The solution was then added 8 L of petroleum ether dropwise at 45 C. The mixture was cooled down slowly to 15-0 C. and stirred for 1 hour. A large precipitate was formed and filtered. The filter cake was dried at 45 C. and 954 g of 3-(trifluoromethyl)-5-(4-methyl-1H-imidazole-1-yl)-benzeneamine of formula I were obtained. (Yield: 47.5%). The obtained compound of formula I had purity of 99.7% on area by HPLC and contained 0.13% on area by HPLC, of the 5 methyl isomer impurity.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Bromo-5-(trifluoromethyl)aniline, its application will become more common.
Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; US2010/16590; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary