Darifenacin is a potent and competitive M 3 selective receptor antagonist (M 3 SRA), and its hydrobromide salt (1) is the active ingredient of pharmaceutical formulations for oral treatment of urinary incontinence. The present work demonstrates an efficient, commercial manufacturing process for darifenacin hydrobromide (1).

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.

Commercial manufacturing of benzphetamine hydrochloride along with its impurity profiling is disclosed. Deoxygenation of pseudoephedrine is reported with ∼100% retention by shielding the amine group as its tert-butyl carbamate, which is very straightforward to eliminate at the end. Four unknown process-related impurities are isolated from the samples of final API and characterized on the basis of their NMR and mass spectral analysis. Structures of the isolated impurities are confirmed by independent syntheses and coinjecting with the isolated one.