SYNTHESIS FOR THE PREPARATION OF QUETIAPINE

摘要

Process for the synthesis of 2-[2-(4-dibenzo[b,f][1,4]thiazepine-11-yl-piperazine-1-yl)-ethoxy]-ethanol of formula (I) (quetiapine) by reacting the 1-oxodibenzo-[b,f][1,4]thiazepine of formula (II) with phosphorus oxychloride by d) using 1-6 molequivalent of phosphorus oxychloride in an inert solvent and the obtained 11-chlorodibenzo[b,f][1,4]thiazepine compound of formula (IV) without isolation; e) is reacted further in an inert solvent in the presence of a base with 2-[2-(1-piperazinyl)-ethoxy]-ethanol dihydrochloride of formula (III a) or dihydrochloride monohydrate of formula (III b), in the mixture of an inert non-polar and dipolar aprotic solvent; f) in desired case the isolated quetiapine base of formula (I) is reacted with fumaric acid to form the hemifumarate salt thereof.