The present invention relates to the process for the preparation and purification of citalopram (I) ##STR1## in which a compound of formula (II) ##STR2## wherein Z is iodo, bromo, chloro or CF.sub.3 --(CF.sub.2).sub.n --SO.sub.2 --O--, n being 0, 1, 2, 3, 4, 5, 6, 7 or 8, is subjected to a cyanide exchange reaction with a cyanide source; the resultant crude citalopram product is optionally subjected to some initial purification and subsequently treated with an amide or an amide-like group forming agent; the reaction mixture is then subjected to an acid/base wash and/or crystallisation and recrystallisation of citalopram in order to remove the amides formed from the crude citalopram mixture; and the resulting citalopram product is optionally further purified, worked up and isolated as the base or a pharmaceutically acceptable salt thereof.
The present invention provides a process for decreasing the content of [1-(3-dimethylamino)propyl)]-1-(4-fluorophenyl)-1,3-dihydro-5-halo-isoben- zofuran, a compound of formula 1, wherein X is halogen, ##STR00001## by converting to a compound of formula 3, ##STR00002## comprising subjecting [1-(3-dimethylamino)propyl)]-1-(4-fluorophenyl)-1,3-dihydro-5-halo-isoben- zofuran present as impurity in crude 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofura- n carbonitrile to hydrogenolysis.
The present invention provides a process for the preparation of crude 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofura- n carbonitrile base with substantially low levels of impurities by arresting the formation of substantial amount of carboxamide impurity, high molecular weight impurities and suppressing the formation of desmethylcitalopram besides taking the cyanide exchange reaction to near completion and thus avoiding an extensive and expensive purification process.
A process for the preparation of citalopram of formula (I) ##STR1## in which a compound of formula (II) ##STR2## wherein Z is iodo, bromo, chloro or CF.sub.3 --(CF.sub.2).sub.n --SO.sub.2 --O-- n being 0, 1, 2, 3, 4, 5, 6, 7 or 8, is subjected to a cyanide exchange reaction in which the group Z is exchanged with cyanide by reaction with a cyanide source; the resultant crude citalopram product is optionally subjected to some initial purification and the crude citalopram base is subsequently subjected to a film distillation process; the resulting citalopram product is then optionally further purified and worked up and isolated as the base or a pharmaceutically acceptable salt thereof.
The invention relates to a method for the preparation of citalopram comprising reaction of a compound of formula II ##STR1## with a compound having the formula ##STR2## wherein R is halogen or --O--SO.sub.2 --X, wherein X is alkyl, alkenyl, alkynyl or optionally alkyl substituted aryl or aralkyl, and R.sup.1 is dimethylamino, halogen, --O--SO.sub.2 --X wherein X is as defined above, provided that R is not halogen when R.sup.1 is dimethylamino; and if R.sup.1 is dimethylamino followed by isolation of citalopram base or a pharmaceutically acceptable acid addition salt thereof, and if R.sup.1 is halogen or --O--SO.sub.2 --X, wherein X is as defined above, followed by conversion of the resulting compound of formula ##STR3## wherein R.sup.2 is halogen or a group of formula --O--SO.sub.2 --X wherein X is as defined above to citalopram, followed by isolation of citalopram base or a pharmaceutically acceptable acid addition salt thereof.
A method for the preparation of citalopram comprising reaction of a compound of formula 5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-i sobenzofuran with an oxidising agent to prepare citalopram.
