P. Solanki, Sekhar Babu Uppelli, B. Pandit
Jan 9, 2013
Citations
0
Influential Citations
10
Citations
Journal
ACS Sustainable Chemistry & Engineering
Abstract
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.