【药物名称】Aminoglutethimide, AG-1, Orimeten, Cytadren
化学结构式(Chemical Structure):
参考文献No.563513
标题:Production of (R)-aminogluthimide: A new route from 1-chloro-4-nitrobenzene
作者:Bunegar, M.J.; et al.
来源:Org Process Res Dev 1999,3(6),442
合成路线图解说明:

An improved procedure for the large-scale preparation of (R)-aminoglutethimide has been reported. Nucleophilic substitution of 1-chloro-4-nitrobenzene (I) with methyl cyanoacetate afforded the (nitrophenyl)cyanoacetate (II), which was alkylated with diethyl sulfate in the presence of Et3N, yielding (III). Hydrolysis and decarboxylation of the cyano ester (III) by means of K2CO3 in aqueous MeOH provided the arylbutyronitrile (IV). Subsequent Michael addition with methyl acrylate gave adduct (V). This was hydrolyzed to the cyano acid (VI), which was further resolved with (-)-cinchonidine, yielding the desired (R)-enantiomer (VII). Acid-catalyzed cyclization of (VII) in boiling toluene generated the glutarimide derivative (VIII). The nitro group of (VIII) was finally reduced to the title amino derivative by hydrogenation over Pd/C.

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