Development of an improved pilot plant synthesis of (2S)-1-{(R)-[1-(cyclopropylsulfonyl)piperidin-4-yl](3-fluoro-phenyl)methyl}-2-methylpiperazinedium hydrobromide

ORGN 692

John Traverse, john.traverse@spcorp.com, Shen-Chun Kuo, Feng Liang, and William Leong. Department of Chemical and Physical Sciences, Schering-Plough Research Institute, 1011 Morris Ave., U-13-2, Union, NJ 07083
(2S)-1-{(R)-[1-(cyclopropylsulfonyl)piperidin-4-yl](3-fluoro-phenyl)methyl}-2-methylpiperazinedium hydrobromide (1) is an intermediate in the synthesis of a drug substance in development. An improved synthesis was developed. A key feature of the process is the trapping of a low-melting, difficult to handle aldehyde as a benzotriazole adduct that has improved physical properties.