A chemical probe for the estrogen receptor: Synthesis of the 3H-isotopomer of raloxifene

Article abstract of DOI:10.1002/jlcr.2580360105

Radiolabelled raloxifene (LY156758) has been prepared by tritium gas hydrogenolysis of a 3-aroyl-bis-brominated precursor. The requisite halogenated intermediate was accessed by regioselective aroylation of benzothiophene 6 with the acid chloride of 3,5-dibromo-4-[2-(1-piperdinyl)ethoxy]benzoic acid (5). Selective deprotection of the aryl methyl ethers in the presence of the ethoxy side-chain followed by palladium catalyzed halogen-tritium exchange provided the target compound with a specific activity of 30.1 Ci/mmol.