Process For The Synthesis Of N-2-(7-Methoxy-1 Naphthyl)Ethyl]Acetamide (Agomelatine)

Abstract

Process for the industrial synthesis of the compound formula (I) which process is characterised in that there is reacted 7 methoxy- 1 -naphthol of formula (II): with which there is condensed, in the presence of palladium, after converting the hydroxy function into a leaving group such as a halogen, tosylate or trifluoromethanesulphonate group, the compound of formula (III): CH2=CH-R (III), wherein R represents the groupwherein R and R", which may be the same or different, each represent a linear or branched (C1-C6)alkyl group or R' and R" together form a (C2-C3)alkylene chain and the ring formed may be fused with a phenyl group, to yield the compound of formula (IV): wherein R is as defined hereinbefore, which is subjected to catalytic hydrogenation to yield the compound of formula (V): wherein R is as defined hereinbefore, which is subjected to base or acid hydrolysis or to a binary reducing agent / acid system to yield the compound of formula (VI) or its hydrochloride salt: which is successively subjected to the action of sodium acetate and then acetic anhydride to yield the compound of formula (I), which is isolated in the form of a solid.