Development of the commercial process for Zoloft/sertraline

Area of Science:

• Organic Chemistry
• Pharmaceutical Development
• Chemical Engineering

Background:

• Sertraline (Zoloft) marked a milestone for Pfizer as its first synthetic drug with non-naturally derived stereocenters.
• Previous Pfizer products like azithromycin and beta-lactams utilized naturally sourced stereocenters.

Purpose of the Study:

• To explore and identify a commercially viable synthetic route for sertraline.
• To investigate the challenges and potential of adopting new technologies in pharmaceutical manufacturing.
• To highlight the successful application of continuous chromatography in chiral drug synthesis.

Main Methods:

• Classical resolution and chromatography were used to isolate the active stereoisomers.
• Exploration of various synthetic strategies, including enantioselective ketone reduction and SN2 displacement for chirality transfer.
• Implementation and evaluation of continuous chromatography for large-scale production.

Main Results:

• Multiple synthetic pathways were investigated for sertraline production.
• Continuous chromatography emerged as the most effective and scalable technology for achieving the desired stereochemistry.
• The development process highlighted significant challenges in integrating novel technologies within the pharmaceutical industry.

Conclusions:

• The successful development of sertraline, utilizing continuous chromatography, demonstrates the viability of advanced separation technologies.
• Continuous chromatography offers a transformative approach for the development of chiral pharmaceuticals.
• This case study provides valuable insights into overcoming technological hurdles in pharmaceutical manufacturing.