A Novel Synthetic Process of Diflunisal

LIU Qiulian

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主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
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Chinese Journal of Pharmaceuticals ›› 2018, Vol. 49 ›› Issue (02) : 172. DOI: 10.16522/j.cnki.cjph.2018.02.007
Paper

A Novel Synthetic Process of Diflunisal

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Abstract

A novel synthetic process of diflunisal (1) was reported. 2-Chloro-5-bromobenzonitrile (3) was prepared via bromination by N-bromosuccinimide from 2-chlorobenzonitrile (2). Then 3 coupled with (2,4-difluorophenyl)boronic acid (4) catalyzed by bis(triphenylphosphine)dichloronickel which formed by nickel
chloride hexahydrate and triphenylphosphine to afford 4-chloro-2',4'-difluoro-(1,1'-biphenyl)-3-carbonitrile (5). Finally, compound 5 was subjected to hydrolysis in autoclave to prepare 1 with an overall yield of 63.1%(based on 2). This new process has some advantages, such as mild reaction conditions and simple operation, which are more suitable for commercial production.

Key words

diflunisal / non-steroidal anti-inflammatory drug / (2,4-difluorophenyl)boronic acid / nickel-catalyzed coupling / synthesis

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LIU Qiulian. A Novel Synthetic Process of Diflunisal. Chinese Journal of Pharmaceuticals. 2018, 49(02): 172 https://doi.org/10.16522/j.cnki.cjph.2018.02.007

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