Pfizer has redesigned the synthesis of several of its pharmaceutical products to reduce generation of hazardous waste.

Changes were made in the synthetic route to sildenafil citrate (see Fig. 9.7), the active ingredient in Viagra® (Dunn et al.,

2004), which resulted in a more efficient process that required no extraction and recovery system for solvent steps (see Fig. 9.8). The E-factor (Sheldon, 1992) for the process is 6 kg

waste/kg product, which is substantially lower than an E-factor of 25–100, which is typical of pharmaceutical processes.

Furthermore, all chlorinated solvents had been eliminated from the commercial process. During the medicinal chemistry stage

in 1990, the solvent usage was 1816 L/kg, and the optimized process used 139 L/kg solvent, which was reduced to 31 L/kg

during commercial production in 1997 and to 10 L/kg with solvent recoveries. Pfizer plans to replace t-butanol/t-butoxide

cyclization with an ethanol/ethoxide cyclization. Combined with other proposed improvements, this is expected to increase the

overall yield from 76–80% and further reduce solvent usage and organic waste.