【摘要】 本研究改进了米洛巴林苯磺酸盐的合成工艺。关键中间体3-乙基双环[3.2.0]庚-3-烯-6-酮(9)与二甲氧基膦酰基乙酸叔丁酯(10)发生Horner-Wadsworth-Emmons反应得到11,11与硝基甲烷在碱催化下发生迈克尔加成反应得到12,12经还原得到内消旋体13(rac),13(rac)通过D-扁桃酸手性拆分后得到14,14经过水解得到15,15最后与苯磺酸成盐得米洛巴林苯磺酸盐(1)。工艺进行改进后,各步反应条件温和,操作简单,原材料便宜易得,总收率为15.67%,产品质量可靠,适合规模化生产。更多还原

【Abstract】 The synthetic process of mirogabalin besylatewas improved in this report. The key intermediate 3-ethylbicyclo [3. 2.0] hept-3-en-6-one( 9) reacts with tert-butyl( dimethoxyphosphoryl) acetate( 10) to afford 11. Michael addition of intermediate 11 with nitromethane in the presence of alkali yields 12. Reduction of 12 gives 13( rac),and then acid chiral separation 13( rac) obtains 14. 14 is hydrolyzed and then treated with phenylsulfonicacid to afford mirogabalin besylate. After the synthetic process is improved,the reaction conditions of each step are mild,and the operation is simple. The raw materials have low cost and easy to obtain,and the total yield was 15. 67%. The improved process is suitable for large-scale production.更多还原