| 主权项 |
1. An improved process for preparation of Rivaroxaban of formula (I), the process comprising:
a) reacting, 4-(4-aminophenyl)morpholine-3-one of formula (II) with 2-[(2S)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione of formula (III) in a first solvent to obtain 2-[(2R)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl]-1H-isoindole-1,3(2H)-dione of formula (IV); b) preparing compound of formula (V) by reacting compound of formula (IV) using a phosgene or phosgene equivalent(s) or anhydrides or bis(aryl) carbonate of formula (XVI) wherein, Ar can be phenyl, substituted phenyl, selected from p-nitrophenyl, 4-(trifluoromethyl)phenyl, 4-cyanophenyl and the like,in a second solvent and optionally in presence of a base; c) eliminating the pthalamide group from compound of formula (V) in the said first solvent using a de-protecting agent to obtain 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one formula (VI); optionally isolating and purifying compound of formula (VI); optionally converting to its acid addition salt; d) reacting compound of formula (VI) or acid addition salt with 5-chlorothiophene-2-carbonyl chloride of formula (VIII) in a third solvent and in presence of a base to obtain Rivaroxaban of formula (I), and isolating compound of formula (I); or optionally, the reaction can be carried out in biphasic medium and optionally in the presence of a phase transfer catalyst. e) optionally, purifying Rivaroxaban of formula (I). |
