Process development of a C-4 methylcarbonate analog of paclitaxcel

ORGN 18

Rajendra Deshpande, Frank Gibson, Edward Gublo, Jason Hamm, Jun Li, jun.li1@bms.com, Jing Liang, and Karen Tenhuisen. Process Research & Development, Bristol-Myers Squibb, One Squibb Dr, New Brunswick, NJ 08903
A practical synthesis of a C-4 methylcarbonate analog of paclitaxcel has been developed. The process improvements will be exemplified in control of impurities and optimization of the final step, which includes telescoped desilylation and hydrogenolysis of a Cbz protecting group, using a DoE statistical design.