Pregabalin manufacturer

A second-generation manufacturing process involving a highly enantio- and diastereo-selective lipase-catalysed kinetic resolution step has recently been reported for the production of pregabalin, a lipophilic y-aminobutyric acid analogue that was developed for the treatment of several central nervous system disorders (Scheme 1.32). ° ... 

The Development of a Creen, Energy Efficient, Chemoenzymatic Manufacturing Process for Pregabalin... 

Several new ligands that possess chirality at the phosphorus center have been developed and shown to be excellent catalysts for the asymmetric reduction of enamides to amino acids and chiral amines and P-enamides to P-amino esters. One ligand that shows great promise to be used at the manufacture scale is Trichickenfootphos, which has demonstrated high activity and enantioselectivity in the production of a chiral intermediate for Pregabalin. 

The manufacturer notes that there was no clinically relevant pharmacokinetic interaction between pregabalin and lorazepam or alcohol, and that concurrent use caused no clinically important effect on respiration. However, they note that pregabalin may potentiate the effects of lorazepam and alcohol. ... 

Under optimized conditions, the enzymatic process was tested for robustness in multiple mns at 10 kg scale. Three pilot runs at 900 kg (1600 L reactor) scale as well as manufacturing trials at 3.5t (8000 L reactor) demonsuated the consistently high performance and scalability of this enzymatic reaction. A heat-promoted decarboxylation of (S)-3 efficiendy generated ethyl ester (S)-4, a known precursor of Pregabalin 1 [34]. 

Martinez, C. A. Hu, S. Dumond, Y. Tao, J. Kelleher, P Tully, L., Development of a chem-oenzymatic manufacturing process for pregabalin. Organic Process Research and Development... 

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