盐酸索他洛尔的合成  

Synthesis of Sotalol Hydrochloride

作　　者：孙登学 章国林[1] 

机构地区：[1]浙江大学药学院,浙江省抗肿瘤药物临床前研究重点实验室,浙江杭州310058 [2]浙江华海药业股份有限公司,浙江临海317000

出　　处：《精细化工》2016年第1期74-77,共4页Fine Chemicals

摘　　要：以苯胺为原料,经过甲磺酰化、傅克酰基化、异丙胺化和氢化还原得到盐酸索他洛尔产品(Ⅰ),总收率达到75.9%(以苯胺计),化学纯度达到99.8%,最终产物结构通过IR、1HNMR、ESI-MS及元素分析进行表征。该文对甲磺酰化工序的缚酸剂进行研究,确定碳酸氢钠最佳摩尔比为n(碳酸氢钠)∶n(苯胺)=1.1∶1,反应温度为室温,收率为97%;对氢化还原反应的钯炭含量、用量和回收套用进行研究,确定7%钯炭最佳用量为中间体IV投料质量的5%,回收钯炭套用最佳次数为3次。该法合成步骤简便,工艺绿色环保,经济适用,非常适合于产业化大生产。Sotalol hydrochloride（ Ⅰ） was prepared from aniline by methylsulfonylation,Friedel –Crafts acylation,isopropylamination and hydrogen reduction. The total yield was up to 75. 9%（ based on aniline）,and the purity was 99. 8%. The structure of the product was confirmed by IR,~1HNMR,ESI-MS and elemental analysis. The deacid-reagents in the methylsulfonylation were studied and found that the optimal reaction condition was n（ sodium bicarbonate） ∶ n（ aniline） = 1. 1 ∶ 1 at ambient temperature with the yield of 97%; The content,amount and recovery of Pd / C in the hydrogen reduction were studied,The optimal weight of 7% Pd / C was 5% of intermediate IV,The optimal reuse number of 7% Pd / C was 3 times. This method is simple,green,economical and suitable for industrial production.

关 键 词：抗心律失常 Β受体阻断剂 盐酸索他洛尔 医药原料 

分 类 号：O625.63[理学—有机化学]