Chapter 5: Synthesis of Raloxifene

Use of hazardous reagents is common in most of the reported synthesis of molecules of various interests. Hazardous reagents at a manufacturing scale pose a great challenge in terms of handling, operation and workups. These reagents are unsafe and found to have proven toxicity (in the majority of the cases). If not avoided, these reagents will defy the purpose of Green Chemistry and sustainability in organic synthesis. In this chapter, the synthesis of raloxifene, [6-Hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]{4-[2-(piperidin-1-yl)eth-oxy] phenyl}methanone hydrochloride 1, an estrogen agonist/antagonist commonly considered as a selective estrogen receptor modulator (SERM), will be discussed considering the evolving trends of switching the usage of hazardous to less hazardous reagents. Raloxifene impedes the re-sorption of bone by reducing the biochemical markers of bone turnover in the premenopausal women thereby helping in the management of osteoporasis. Raloxifene hydrochloride also lowers the chances of developing a certain type of breast cancer (invasive breast cancer) in post-menopausal women.