Torcan Chemical Ltd

Raymond So

Yee-Fung Lu

Jan Oudenes

Clarke Slemon

Teng-Ko Ngooi

Casimir G Antczak

Dan To

Cisapride, i.e. cis-4-amino-5-chloro-N-�1-�3-(4 fluoro-phenoxy)propyl!-3-methoxy-4-piperidinyl!-2-methoxy-benzamide, and similar benzamide derivatives, are prepared from novel 1-aryloxyalkyl- or 1-aralkyl-3-arylcarbonyloxy-4-oxo-piperidines, by nuclear substituent re arrangement involving acyl transfer under animal forming conditions, to give the corresponding 1-aryloxyalkyl- or 1-aralkyl-3-hydroxy-4-lower alkoxy-4-arylamido piperidine. This in turn is readily converted to the corresponding 3-oxo-4-arylamido-piperidine by reaction with strong organic acid, which can then be reduced, deprotected and 3-methylated to give the final compound, e.g. cisapride.

Preparation of cisapride

In a process for making synthetic prostaglandin-type compounds such as misoprostol, organo metallic cuprate complexes capable of reacting with cyclopentenones are prepared by reaction of an alkyl lithium compound with a cuprous halide, followed by reaction of the resulting complex with a vinyl stannane, using an excess of alkyl lithium in the initial reaction and maintaining the excess present during the formation of the organo metallic cuprate complex.

Misoprostol

Cisapride, i.e. cis-4-amino-5-chloro-N-[1-[3-(4 fluoro-phenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxy-benzamide, and similar benzamide derivatives, are prepared from novel 1-aryloxyalkyl- or 1-aralkyl-3-arylcarbonyloxy-4-oxo-piperidines, by nuclear substituent re arrangement involving acyl transfer under animal forming conditions, to give the corresponding 1-aryloxyalkyl- or 1-aralkyl-3-hydroxy-4-lower alkoxy-4-arylamido piperidine. This in turn is readily converted to the corresponding 3-oxo-4-arylamido-piperidine by reaction with strong organic acid, which can then be reduced, deprotected and 3-methylated to give the final compound, e.g. cisapride.

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Richmond Hill, Canada

Raymond So