PROCESS FOR THE PREPARATION OF RACEMIC CITALOPRAM AND/OR S- OR R-CITALOPRAM BY SEPARATION OF A MIXTURE OF R- AND S-CITALOPRAM

• Main Authors: RIKKE EVA HUMBLE, MICHAEL HAROLD ROCK, OLE NIELSEN, TROELS VOLSGAARD CHRISTENSEN, ROBERT DANCER, HANS PETERSEN
• Format: Patent
• Language: Croatian; English
• Published: 31.12.2011
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Postupak za pripravljanje slobodne baze racemičnog citaloprama ili njegove kiselinske soli i/ili R- ili S-citaloprama kao slobodne baze ili njihove kiselinske soli separacijom mješavine R- i S-citaloprama s više od 50% jednog od enantiomera u frakciju koja se sastoji od racemičnog citaloprama i/ili frakciju S-citaloprama ili R-citaloprama, naznačen time, da sei) citalopram taloži iz otapala kao slobodna baza ili njezina kiselinska sol; ii) dobiveni talog odvoji iz matične tekućine; iia) ako je talog u kristalnom obliku, on se po želji jednom ili više puta rekristalizira radi stvaranja racemičnog citaloprama, a potom se po želji pretvara u njegovu kiselinsku sol; iib) ako talog nije u kristalnom obliku, koraci i) i ii) se po želji ponavljaju sve dok se ne dobije talog u kristalnom obliku, a on se po želji jednom ili više puta rekristalizira radi stvaranja racemičnog citaloprama, a potom se po želji pretvara u njegovu kiselinsku sol; iii) matična tekućina se po želji podvrgava daljnjem pročišćavanju te se iz matične tekućine izoliraju S-citalopram ili R-citalopram i po želji pretvaraju u njihovu kiselinsku sol. Patent sadrži još 18 patentnih zahtjeva. The invention relates to a process for the preparation of racemic citalopram free base or an acid addition salt thereof and/or R- or S-citalopram as the free base or an acid addition salt thereof by separation of a mixture of R- and S-citalopram with more than 50% of one of the enantiomers into a fraction consisting of racemic citalopram and/or a fraction of S-citalopram or R-citalopram characterized in that i) citalopram is precipitated from a solvent as the free base or as an acid addition salt thereof; ii) the precipitate formed is separated from the mother liquor; iia) if the precipitate is crystalline it is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iib) if the precipitate is not crystalline, steps i) and ii) are optionally repeated until a crystalline precipitate is obtained and the crystalline precipitate is recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iii) the mother liquor is optionally subjected to further purification and S-citalopram or R-citalopram is isolated from the mother liquor and optionally converted into an addition salt thereof.