Electric Literature of 656-64-4,Some common heterocyclic compound, 656-64-4, name is 3-Bromo-4-fluoroaniline, molecular formula is C6H5BrFN, 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.
A 500 mL three-necked flask was charged with benzophenone (79.8 g, 0.438 mol), trimethyl orthoformate (69.6 g,0.656 mol), p-toluenesulfonic acid (3.4 g, 0.02 mol) and methanol300mL, open the stirring, heat to reflux, heat for 3 hours, cool down and dilute the solvent under reduced pressure, add the product obtained in the previous step (62.4g, 0.438mol) and 300mL of toluene, increase to 80-110 degrees for 3 hours, increase the temperature The solvent was distilled off under normal pressure until the disappearance of the starting material by GC. The temperature was lowered, and the solvent was concentrated under reduced pressure to give a crude product 136.2 g, dissolved in 1.2 L acetonitrile, transferred to a 2 L reaction flask, and tetrabutylammonium bromide (282.1 g, 0.875) was added. Mol), copper bromide (0.98g, 0.004mol), tert-butyl nitrite (54.1g, 0.525mol) was added dropwise at 0-10 C, stirred at room temperature for 6 hours, TLC controlled material was completely reacted, hydrogen peroxide was added dropwise Sodium (73.5 g, 0.875 mol) dissolved in 600 mL of water, followed by 3-bromo-4-fluoroaniline (124.7 g, 0.656 mol), heated to 50 C, stirred for 1 hour, TLC controlled raw material reaction was complete, cooling , joinThe mixture was combined with EtOAc (EtOAc m.The obtained crude product was recrystallized from ethyl acetate / n-hexane to afford 137.4 g.Yield 65.4%
The synthetic route of 656-64-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Shanghai Jinlu Pharmaceutical Technology Co., Ltd.; Gao Feng; Zeng Sailan; Jiang Junqiang; Zhang Xingxing; (8 pag.)CN108003112; (2018); A;,
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