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A practical scalable chemoenzymatic process was developed for the synthesis of (R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (2) (R‐CMHA) and achieved 98.5% ee and 99% HPLC purity at pilot scale. The systematic statistical design of experimentation (DOE) of esterification, enzymatic desymmetrization and CaCl2 assisted amidation led to the robust design space.

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.