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[1]张更真.来那度胺中间体的水相合成[J].武汉工程大学学报,2012,(05):20-22,60.[doi:103969/jissn16742869201205006]
　ZHANG Geng\|zhen.Synthesis of Lenalidomide intermediates in water[J].Journal of Wuhan Institute of Technology,2012,(05):20-22,60.[doi:103969/jissn16742869201205006]
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
期数:
2012年05期
页码:
20-22,60
栏目:
化学与化学工程
出版日期:
2012-05-31

文章信息/Info

Title:
Synthesis of Lenalidomide intermediates in water
文章编号:
6742869(2012)05002003
作者:
张更真
浙江贝得药业有限公司，浙江 绍兴 312071
Author(s):
ZHANG Geng\|zhen
Zhejiang Better Pharmaceuticals Company Limited，Shaoxing 312071,China
关键词:
来那度胺中间体; 溴化; 绿色介质; 产率
Keywords:
lenalidomide intermediates; bromination; green medium; yield
分类号:
TM 344.1
DOI:
103969/jissn16742869201205006
文献标志码:
A
摘要:
传统的N-溴代丁二酰亚胺（NBS）α\|溴代反应是用光引发偶氮二异丁腈（AIBN）产生自由基，在四氯化碳或者其它氯化有机溶剂中进行.在水介质中，采用加热到80～85 ℃、控制搅拌速度为20～30 r/min产生自由基引发α\|溴代反应的方法合成来那度胺中间体：2\|溴甲基\|3\|硝基苯甲酸甲酯.该反应条件下2\|甲基\|3\|硝基苯甲酸甲酯转变为熔融态，在水中形成两相，目标产物产率可达80%，纯度为93%.不需要光照和有毒溶剂，2\|溴甲基\|3\|硝基苯甲酸甲酯容易通过可变速度搅拌和耐酸设备进行工业化生产.
Abstract:
N\|bromosuccinimide (NBS) side\|chain bromination reaction of alkyl arenes was traditionally conducted by lighting\|initiated azobisisobutyronitrile (AIBN) generating free radicals in CCl4 or other chlorinated solvents. In the water medium, by heating to 80~85 ℃ with the stirring rate of 20~30 r/min, the generated free radicals initiated α\|bromination to synthesize Lenalidomide intermediates: 2\|Bromomethyl\|3\|nitrobenzoic acid methyl ester; methyl 2\|methyl\|3\|nitrobenzoate became molten state and two\|phases were formatted in water; the yield of the aimed product is up to 80% with purity of 93%. Without lighting and toxic solvents, 2\|Bromomethyl\|3\|nitrobenzoic acid methyl ester is easily industrialized in variable speed mixing and anti\|acid equipment.

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备注/Memo

备注/Memo:
收稿日期：20120405作者简介：张更真（1977-），男，山东菏泽人，工程师.研究方向：抗肿瘤类药物.
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