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 450-91-9 as follows. Safety of 4-Fluoro-2-methoxyaniline
In a flask equipped with a water cooled condenser a phenyl amine (1.0 equiv.), bis(2- chloroethyl)amine hydrochloride (1.5 equiv.), potassium carbonate (1.5 equiv.) and sodium iodide (0.4 equiv.) were suspended in diglyme. The resulting reaction mixture was allowed to heat to reflux over a period of one hour and allowed to stir at reflux for an additional 2.5 hours. It was then partitioned between dichloromethane and distilled water. The pH of the water layer was adjusted to basic pH (9-10) with 5% aqueous sodium hydroxide. The water phase was extracted thrice with dichloromethane. The combined organic layers were washed once with 10% aqueous sodium thiosulfate to remove iodine, dried over anhydrous sodium sulfate and the solvent removed in vacuo. The product was purified by column chromatography in 2M ammonium/methanol and dichloromethane mixtures.; l-(4-Fluoro-2-methoxy-phenyl)-piperazine was synthesized from 4-Fluoro-2-methoxy- phenylamine (151.5 mg, 1.07 mmol), bis(2-chloroethyl)amine hydrochloride (287.4 mg, 1.61 mmol), potassium carbonate (222.5 mg, 1.61 mmol) and sodium iodide (64.5 mg, 0.43 mmol) in diglyme. Column chromatography 10% 2M ammonia/methanol in dichloromethane provided the product as a dark brown oil (89.8mg, 40%). 1H NMR (300 MHz, CDCl3): delta(ppm) 6.78-6.90(m, IH), 6.57-6.65(m, 2H), 3.86(s, 3H), 3.14(broad t, 2H), 3.05(broad t, 4H), 2.95(t, IH), 2.72(broad t, 2H).
According to the analysis of related databases, 450-91-9, the application of this compound in the production field has become more and more popular.
Reference:
Patent; ASTRAZENECA AB; NPS PHARMACEUTICALS, INC.; WO2006/71730; (2006); A1;,
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