Efficient Synthesis of the Immunomodulating Compound KRP-203

A practical and concise synthesis of KRP-203 ( 1) was achieved by utilizing a palladium coupling reaction mediated by XantPhos and Pd 2 (dba) 3 as the key step. The coupling reaction of aryl bromide 5 with 3-hydroxythiophenol ( 6) proceeded chemoselectively to give phenol 7 in spite of the presence of a chlorine substituent on 5 and a hydroxyl group on 6. Phenol 7 was converted into KRP-203 by benzylation and removal of the protecting groups in high yield.