An efficient, short manufacturing process for fenspiride hydrochloride is reported. Nitro-aldol condensation is the key reaction in the developed process. Improved routes to key building blocks are demonstrated by expedient multikilogram production. Hazardous reactions are avoided. API produced following this new route meets the quality requirement NLT 99.70% purity by HPLC with any individual impurity NMT 0.10% with very good yield.

A safe and inexpensive procedure for asymmetric reduction of ketones using in situ prepared N,N-diethylaniline borane (DEANB) and oxazaborolidine catalyst from sodium borohydride, N,N-diethylaniline hydrochloride and (S)-α,α-diphenylprolinol is described. This protocol is demonstrated successfully to manufacture enantiopure dapoxetine at the plant scale.

An impurity formation during the nitro group reduction for the synthesis of Olsalazine Sodium API, which was later explored for the development of a short and efficient manufacturing process for tricaine mesylate is reported here. The highlight of the synthesis is, during the nitro group reduction, the deoxygenation occurs forming the core of tricaine and the leaving mesyloxy group serves as a counter anion furnishing the tricaine mesylate in one step. The reported process here circumvents the need for isolation of the free base and a separate salt formation step, thus it is more economical and efficient.

An improved synthesis of chirally pure advanced pyrrolidone intermediate of the (S)-(+)-vigabatrin, an antiseizure active pharmaceutical ingredient (API) is reported. The synthesis is developed using commercially available, cheaper amino acid (R)-methionine. Meldrum’s acid served as a two-carbon homologation unit to access the pyrrolidone intermediate in a short synthetic sequence. The sequence to pyrrolidone intermediate is scalable and eludes the use of organometallic pyrophoric reagents on a large scale.