New process for synthesizing (7-methoxy-1-naphtyl)acetonitrile and its application in the synthesis of agomelatine

摘要

Producing 2-(7-methoxy-1-naphthyl)acetonitrile (I) comprises reacting 7-methoxy-1-tetralone (IV) with cyanoacetic acid in the presence of an organoammonium carboxylate catalyst (VI) while removing water and contacting the resulting 2-(7-methoxy-3,4-dihydro-1-naphthyl)acetonitrile (VII) with a hydrogenation catalyst in the presence of an allylic compound. Producing 2-(7-methoxy-1-naphthyl)acetonitrile of formula (I) comprises reacting 7-methoxy-1-tetralone (IV) with cyanoacetic acid in the presence of an organoammonium carboxylate catalyst of formula (VI) while removing water and contacting the resulting 2-(7-methoxy-3,4-dihydro-1-naphthyl)acetonitrile of formula (VII) with a hydrogenation catalyst in the presence of an allylic compound. R, R' = 3-10C alkyl, aryl or aryl(1-6C alkyl), where aryl is selected from phenyl, naphthyl or biphenylyl (all optionally substituted by 1-3 1-6C alkyl, OH or 1-6C alkoxy). Independent claims are also included for: (1) producing agomelatin by production of (VII) as above followed by aromatization, reduction and reaction with acetic anhydride; (2) producing agomelatin by production of (I) as above followed by reduction and reaction with acetic anhydride. [Image].