6-氟-5-甲氧基吲哚合成工艺研究

Study on the synthetic technology of 6-fluoro-5-methoxy-1H-indole

以3-氟-4-甲氧基苯胺、水合氯醛和盐酸羟胺为原料,通过Sandmeyer异亚硝基乙酰替苯胺合成法制备得6-氟-5-甲氧基靛红,再经过硼氢化钠/三氟化硼乙醚体系还原制备得6-氟-5-甲氧基吲哚。考察了酰胺化反应温度和反应时间、成环反应温度及还原体系对反应收率的影响,通过1HNMR、13CNMR、元素分析等手段对产品结构进行了表征。较佳的酰胺化反应温度和反应时间为90℃回流反应2min,较优的成环反应温度为65℃,选用更加安全的硼氢化钠/三氟化硼乙醚体系作为还原剂。本文首次报道了由6-氟-5-甲氧基靛红还原制备6-氟-5-甲氧基吲哚的工艺,与现有6-氟-5-甲氧基吲哚合成工艺相比,避免了使用剧毒品,具有更安全,反应条件温和,步骤少,操作简便,总收率较高(54.96%),成本较低的优点,适合批量制备5-甲氧基-6-卤代吲哚,具有广阔的工业应用前景。

6-Fluoro-5-methoxy-1H-Isatin was prepared with Sandmeyer isonitrosoacetanilide isatin synthesis method using 3-fluoro-4- methoxyaniline, the chloral hydrate and the hydroxy-lamine hydroehloride as raw materials, then were reduced to 6-Fluoro-5-methoxy- 1H-indole through NaBH4/BF4-Et20 reduction system. The effects of acetylation reaction temperature and time, annulation reaction temperature,reduetants on the yield of indole were investigated. All products＇ structures were characterized by 1HNMR,53 CNMR and elemental analysis. The modified reaction temperature and time to acetylation reaction, reaction temperature to annulation reac- tion, better reductant were 90℃ （reflux） for 2in,65 ~C and sodium bomhydride/bomn trifluoride etherate, respectively. The prepa- ration for 6-fluoro-5-methoxyindole reduced from 6-fluoro-5-methoxyisatin was first reported. Compared with the reported synthesis process of 6-fluoro-5-methoxyindole, the improved synthesis process was more convenient, safer with mild reaction conditions, low cost, high yield （The total yield was 54.96% ）and good prospects for industrial applications.