An Improved and Efficient Process for the Production of Highly Pure Paliperidone, a Psychotropic Agent, via DBU Catalyzed N‑Alkylation

The present work describes an improved and efficient process for the synthesis of paliperidone (1), an antipsychotropic agent. The synthesis comprises the DBU (1,8-diazabicycloundec-7-ene) catalyzed N-alkylation of 3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]-pyrimidin-4-...

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Bibliographic Details
Published in:ACS sustainable chemistry & engineering 2013-02, Vol.1 (2), p.243-248
Main Authors: Solanki, Pavankumar V, Uppelli, Sekhar Babu, Pandit, Bhushan S, Mathad, Vijayavitthal T
Format: Article
Language:English
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Summary:The present work describes an improved and efficient process for the synthesis of paliperidone (1), an antipsychotropic agent. The synthesis comprises the DBU (1,8-diazabicycloundec-7-ene) catalyzed N-alkylation of 3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]-pyrimidin-4-one (5) with 6-fluoro-3-piperidin-4-yl-1,2 benzisoxazole hydrochloride (6) in methanol as the solvent and diisopropylamine as a base to yield paliperidone (1) with 85% yield and over 97% purity by HPLC. The present work also describes an industrially efficient purification process for the removal of critical process related impurities (8 and 9) in paliperidone (1). The process furnished 1 with an overall yield of about 60% and 99.85% purity.
ISSN:2168-0485
2168-0485
DOI:10.1021/sc3000916