Solvent Use in Process Development

The initial medicinal chemistry route for the early syntheses of sildenafil required -1540 kg solvent/kg API. After four years of development, a modified chemical route and process led to a 93.9% reduction in the total amount of solvent used. The continued optimization of the sildenafil process as it went into commercial production further reduced the amount of solvent used from 94 to 19 kg solvent/kg API. Several highly hazardous solvents were also eliminated from the production scheme including DCM, methanol, and diethyl ether. Upon implementation of solvent recovery, the total amount of solvent required was only 5 kg solvent/kg API produced [17, 20]. The final commercial route used only 0.32% of the total solvent used for the initial synthesis. 

Slater and Savelski note similar trends in solvent use and waste reduction for a new oncology drug under development at BMS [1]. They indicate that the best opportunities to make a process greener occur in the early stages of drug develop- 

Commercial Commercial Future Target Route-1998 Route-2005 

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