Process for the preparation of 2-(4-Alkyl-1-Piperazinyl)-Benzaldehyde and -Benzylidenyl compounds by Nucleophilc Aromatic Substitution of 2-Fluorobenzaldehyde with 4-Alkyl-1-Piperazine in Water as Solvent.

摘要

The present invention provides a process for the preparation of a citric acid salt of a compound of formula II:
wherein R 1 and R 2 have the meanings given in the specification, comprising the steps of:
(i) allowing a compound of formula III, described herein, to react with a compound of formula IV, described herein, in the presence of a metal carbonate and wherein said process is characterized by the use of water as solvent, excluding mixtures of water and organic solvents; to form a compound of formula I, described herein;
(ii) reacting the compound of formula I as formed in step (i) with an acyl chloride or hydrochloric acid dissolved in an aqueous alkanol;
(iii) reacting the hydrochloride salt of the compound of formula I formed in step (ii) in the presence of a base in a suitable solvent with a compound of formula V, described herein, to form the compound of formula II; and
(iv) mixing the compound of formula II and citric acid in a suitable solvent to form a citric acid salt.