Bermoprofen, AD-1590, Dibenon
Chemical Name: 2-(8-Methyl-10,11-dihydro-11-oxodibenz[b,f]oxepin-2-yl)propionic acid; 10,11-Dihydro-alpha,8-dimethyl-11-oxodibenz[b,f]oxepin-2-acetic acid
CAS No. 72619-46-6 (K salt, racemic), 72619-34-2 (racemate)
项目整合开发状态: Pre-Registered
项目研究机构: Dainippon Pharmaceutical (Originator)
合成路线:The reaction of 2-iodo-5-methylbenzoic acid (I) with 4-hydroxyacetophenone (II) by means of K2CO3 in nitrobenzene at 150 C gives 2-(4-acetylphenoxy)-5-methylbenzoic acid (III),which by reduction with LiAlH4 in refluxing THF is converted into 2-[4-(1-hydroxyethyl)phenoxy]-5-methylbenzyl alcohol (IV).The reaction of (IV) with SOCl2 in refluxing CHCl3 affords 2-[4-(1-chloroethyl)phenoxy]-5-methylbenzyl chloride (V),which is treated with NaCN in refluxing dioxane ethanol-water yielding the dinitrile (VI).The hydrolysis of (VI) with KOH in refluxing ethanol-water gives 2-[4-[2-(carboxymethyl)-4-methylphenoxy]phenyl]propionic acid (VII),which is finally cyclized by treatment with polyphosphoric acid (PPA) at 120 C.
📌 参考资料/链接：
参考文献标题:AD-1590
文献作者:Serradell,M.N.; Arrigoni-Martelli,E.; Castar,J.
参考来源:Drugs Fut 1984,9(6),399
📄 详细内容
合成路线:The reaction of 2-iodo-5-methylbenzoic acid (I) with 4-hydroxyacetophenone (II) by means of K2CO3 in nitrobenzene at 150 C gives 2-(4-acetylphenoxy)-5-methylbenzoic acid (III),which by reduction with LiAlH4 in refluxing THF is converted into 2-[4-(1-hydroxyethyl)phenoxy]-5-methylbenzyl alcohol (IV).The reaction of (IV) with SOCl2 in refluxing CHCl3 affords 2-[4-(1-chloroethyl)phenoxy]-5-methylbenzyl chloride (V),which is treated with NaCN in refluxing dioxane ethanol-water yielding the dinitrile (VI).The hydrolysis of (VI) with KOH in refluxing ethanol-water gives 2-[4-[2-(carboxymethyl)-4-methylphenoxy]phenyl]propionic acid (VII),which is finally cyclized by treatment with polyphosphoric acid (PPA) at 120 C.
参考文献标题:Dibenz[b,f]oxepin and dibenzo[b,f]thiepin derivatives,process for preparation thereof,method of using the same,and compositions thereof
文献作者:Uno,H.; Nagai,Y.; Nakamura,H.
参考来源:EP 0003893; ES 477791; JP 1393170C; JP 54122284; US 4238620
产品链接: CAS No.72619-34-2››