J. Sakaguchi et al., An improved synthesis of butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224), CHEM PHARM, 49(6), 2001, pp. 788-790
A new and facile route for the synthesis of the novel gastrointestinal prok
inetic butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineaceta
te (1b), which exhibited potent gastro- and colon-prokinetic activities by
oral administration without significant side effects, was established. The
key intermediate, butyl 4-amino-1-piperidineacetate (16), was prepared from
commercially available 4-amino-1-benzylpiperidine (2) in a high yield with
four steps. Compound 1b was prepared by condensation of commercially avail
able 4-amino-5-choloro-2-methoxybenzoic acid (7) with 16 in 84% yield. This
improved synthetic route was appropriate for large-scale synthesis of 1b.