Process Development of Citalopram/Escitalopram Oxalate: Isolation and Synthesis of Novel Impurities

Abstract

During process optimization of Escitalopram oxalate novel impurities, 6 and 7 were observed, which were isolated and characterized, and the proposed structure was confirmed by chemical synthesis. Investigation of the cause of impurities formation improved the yield and purity of the drug product during the bulk API synthesis.

Ruthenium‐catalyzed asymmetric ene‐yne metathesis

“…To expand the scope of the reaction, the preparation of oxepine and oxocine derivatives was envisioned. For that purpose, a series of substrates 8 a-g was submitted to metathesis optimized reaction conditions (entries [8][9][10][11][12][13][14]. Interestingly, the formation of O-containing seven-membered ring scaffolds was achieved in good to excellent yields.…”

“…Reaction scope note, this scaffold is encountered in Citalopram, a selective serotonin reuptake inhibitor used as antidepressant agent. [8] After optimization of the desymmetrization reaction, Hoveyda-type chiral ruthenium pre-catalysts Ru-1 and Ru-2, were prepared following procedures of the literature (Scheme 4). [2a] In contrast to the analogous chiral complexes prepared by Grubbs et al from Ru complex G-1, which were described as single stereoisomers, [9] in the present study a mixture of two stereoisomers was observed in the 1 H NMR spectra (60 : 40 ratio for Ru-1 and 75 : 25 ratio for Ru-2).…”

“…Moreover, a one‐pot cycloaddition/oxidation sequence was performed to access the 1,1‐disubstituted 1,3‐dihydroisobenzofuran 13 in 53 % yield. Of note, this scaffold is encountered in Citalopram, a selective serotonin reuptake inhibitor used as antidepressant agent [8] …”