Development and execution of a safe, continuous process for a potentially hazardous oxidation reaction

ORGN 423

Lori A. Spangler, lori.spangler@bms.com1, Mourad Hamedi, mourad.hamedi@bms.com1, Thomas L LaPorte, thomas.laporte@bms.com1, John E. Thornton, john.thornton@bms.com2, Jaan A. Pesti, jaan.pesti@bms.com1, Jale Muslehiddinoglu, jale.muslehiddinoglu@bms.com1, and Ioannis Valvis1. (1) Process Research and Development, Bristol-Myers Squibb Company, Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, (2) Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000
The development of a continuous process that permits oxidation to cleave a carbon-carbon bond on large scale is described. This permits a safe, efficient route to heterocycle 1, which is a key intermediate in the synthesis of a novel drug candidate. Process scouting demonstrated the most efficient route to 1 was via oxidation of the carbon-carbon bond of 2 to yield the critical carbon-oxygen bond. Hazard evaluation of the oxidation demonstrated potential for thermal run-away. Optimization of the oxidation step, safe scale up and successful technical transfer of the continuous process to a vendor will be described.

 

Process R&D and Practical Syntheses of Medicinal Agents
1:00 PM-4:40 PM, Tuesday, 12 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006