氢溴酸沃替西汀生产新工艺

目的 建立制备氢溴酸沃替西汀的新工艺.方法 以2,4-二甲基苯硫酚、2-溴碘苯和哌嗪为起始物料,以双(二亚苄基丙酮)钯为催化剂、1,1′-联苯-2,2′-双二苯膦为配体、叔丁醇钠作为碱,经过2步偶联反应制得沃替西汀,最后与氢溴酸成盐生成氢溴酸沃替西汀.结果 使用该工艺制备得到淡黄色固体8.17 kg,所得化合物经Mass和1H-NMR确证为1-{2-(2,4-二甲基苯基)巯基]苯基}-哌嗪氢溴酸盐(即氢溴酸沃替西汀),摩尔总收率为58.02%,色谱纯度>99.5%.结论 本方法操作简便,收率稳定,产品质量较高,适合工业化生产.

New production technology of vortioxetine hydrobromide

Objective To establish new technology for the production of vortioxetine. Methods Vortioxetine was synthesized by two coupling reaction with 2, 4-dimethylbenzenethiol, 2-bromo-iodobenzene and piperazine as raw materials, ( ±)-2, 2′-bis( diphenylphosphino) -1, 1′-binaphthalene as the ligand, sodium tert-butoxide as base and bis ( dibenzylideneacetone ) palladium as the catalyst. Finally, Vortioxetine hydrobromide was prepared from vortioxetine and hydrobromic acid by salification. Results 8.17 kg yellow solid of 1-﹛2- ( 2, 4-dimethylphenyl ) thio ] phenyl﹜ piperazine hydrobromide ( vortioxetine hydrobromide ) was obtained and confirmed by Mass and 1 H-NMR data with total molar yield of 58. 02% and chromatographic purity of more than 99. 5%. Conclusion The synthesis process is simple and suitable for industrial production, which could provide the product with stable yield and high quality.