These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-1-chloro-4-(trifluoromethyl)benzene, its application will become more common.
Electric Literature of 454-78-4,Some common heterocyclic compound, 454-78-4, name is 2-Bromo-1-chloro-4-(trifluoromethyl)benzene, molecular formula is C7H3BrClF3, 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.
Step 1: To a 500 mL three-neck RBF equipped with a magnetic stirring bar were added, under N2 atmosphere, 3-bromo-4-chloro-benzotrifluoride (16.5 mL, 110 mmol) and dry THF (150 mL). The resulting solution was cooled to 0 C. To this solution was added z’-PrMgBr (110 mL, 110 mmol) and the reaction was warmed to rt and stirred for 1 h. To another 500 mL RBF containing a solution of CuBr Me2S (18.8 g, 91.5 mmol) in THF (100 mL) was added BF3*OEt2 (14 mL, 110 mmol) dropwise at -40 C. The resulting solution was stirred at that temperature for 45 min. Then, the Grignard reagent prepared previously was added dropwise to this solution while maintaining the internal temperature at -32 to -38 C. After completion of addition, the reaction mixture was stirred at that temperature for 1 h. The reaction mixture was cooled to -78 C, and a solution of (2S)-l-t-butyl 2-ethyl 5-methoxypyrrolidine-l ,2- dicarboxylate (25.0 g, 91.5 mmol) in THF (50 mL) was added dropwise. The resulting reaction mixture was allowed to warm up to rt and was stirred for 14 h. The reaction mixture was cooled to 0 C, and saturated aqueous NH4C1 solution (100 mL) was added followed by aqueous NH4OH solution (100 mL) and water (300 mL). The layers were separated. The aqueous layer was extracted with EtOAc (3 x 200 mL). The combined organics were dried over anhydrous Na2S04 and concentrated. The crude product was purified by column chromatography eluting with 5% EtOAc in petroleum ether to yield (2S,5S)-l-tert-butyl 2-ethyl 5-(2-chloro-5- (trifluoromethyl)phenyl)pyrrolidine-l,2-dicarboxylate (34.0 g, 79.8 mmol) as a colorless liquid. 1H NMR (400 MHz, CDC13) 7.32-7.47 (m, 3 H), 5.39-5.50 (m, 1 H), 4.58-4.70 (m, 1 H), 4.22- 4.28 (m, 2 H), 2.55 (m, 1 H), 2.18 (m, 1 H), 2.05 (m, 1 H), 1.83 (m, 1 H), 1.16-1.43 (m, 12 H); LC-MS ESI calc’d. for Ci9H23ClF3N04 [M-Boc]+ 321.84, found 322.2.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-1-chloro-4-(trifluoromethyl)benzene, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; SHAO, Pengcheng Patrick; KRIKORIAN, Arto, D.; VACHAL, Petr; WO2015/17302; (2015); A2;,
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