380580 Development of a Multistep Continuous Process and Manufacturing for a Key Pharmaceutical Intermediate of Dapagliflozin

Monday, November 17, 2014: 12:30 PM
202 (Hilton Atlanta)
Chenchi Wang1, Prashant Deshpande1, Junying Fan2 and Laurent Lehmann1, (1)Research and Development, Bristol-Myers Squibb Company, New Brunswick, NJ, (2)Chemical Development, Bristol-Myers Squibb Co., New Brunswick, NJ

While conventional batch possessing dominates most API-related pharmaceutical manufacturing operations, continuous processing technology has been attracting increased attention due to  its inherent benefits such as enhanced mass and heat transfer, precisely-controlled reaction times, and the use of small reactors.  In the synthesis of Dapagliflozin, the preparation of a key pharmaceutical intermediate, BMS-587319, by common batch processing requires cryogenic conditions to ensure acceptable stability and yield of certain reactive species.  To overcome potential challenges for scale-up on cryogenics requirement and process efficiency, a continuous process was later developed and demonstrated successfully on scale to convert the low-temperature synthesis to an energy-efficient, non-cryogenic operation.  In addition to these manufacturing advantages, the continuous flow production consistently delivered comparable product quality and yield to the batch process over multiple campaigns.  In this presentation, laboratory development, scale-up and production of BMS-587319 by continuous processing will be discussed.

Extended Abstract: File Not Uploaded