Base-Promoted Isomerization of cis-Lactam to trans-Lactam of Asenapine and Optimization of Crystallization Process of Asenapine Maleate Salt: An Antipsychotic Drug

摘要

We have described the development of commercially scalable synthetic process for Asenapine, an antipsychotic drug. This involved the isomerization of cis-lactam compound 5 to required trans-lactam compound 6 and followed by isolation without chromatographic technique. The isolation process was executed up to 10 kg batch scale and achieved with good yield and high purity of trans-lactam compound 6. We have also developed a crystallization process to obtain the stable and pure microcrystalline monoclinic form of asenapine maleate even after micronization with desirable particle size, which was previously unpredictable from the reported crystallization process.