Improved Process for Paroxetine Hydrochloride Substantially Free from Potential Impurities

Abstract

An efficient process for production of paroxetine hydrochloride hemihydrate 1, a selective 5-hydroxytryptamine (serotonin) reuptake inhibitor, is described. Identification and control of potential impurities and establishment of efficient downstream workup procedures enabled us to produce paroxetine hydrochloride hemihydrate 1 efficiently.

GRAPHICAL ABSTRACT

Keywords:

• ICH
• impurities
• process development
• serotinin

ACKNOWLEDGMENT

We thank the management of Dr. Reddy's Laboratories Ltd. for supporting this work.

Notes

^a RRT, relative retention time.

Note. 0.29 RRT PCF; 0.48 RRT PCF TEA salt. A, before addition of TEA; B, after addition of TEA.

Note . Yield with respect to paroxetine free base.

^a Purity by HPLC (%).

Note. SMI, single maximum impurity; ND, not detected.

^a During the reaction, the samples (significant quantity) for analysis were collected at different intervals and as a result comparatively poor yields were obtained.

Note. The contents of 2, 7, 9, 14, and 15 impurities were not detected by HPLC; the level of chiral 16 impurity was detected up to 0.006% by chiral HPLC; the content of 19 found to be less than 1 ppm by LC-MS analysis.

^a MeOH, IPA, and EtOAc were not detected by gas chromatography.

Note. MsOH, methane sulfonic acid.

^a Purities for 7, 1, and the salt of 1 were not reported.

^b Intermediates 7 and 1 were not isolated.

^cIn the improved process, methane sulfonic acid salt of 1 was not prepared.

Communication No. IPDO-IPM-00218.