Description:
An efficient method for the construction of the 5-fluoro-4-hydroxypentyl side chain common to a number of synthetic cannabinoid metabolites was developed. A series of hydroxyl protecting groups was examined to assess the viability as orthogonal protecting groups for epoxidation and regioselective hydrofluorination. The 1-[5-fluoro-4-(diphenyl-tert-butylsilyloxy)]pentyl tosylate was prepared in 67% overall yield (six steps) from pent-4-en-1-ol and was employed for the synthesis of the 4-hydroxy metabolites of the synthetic cannabinoid 5F-APINACA and CUMYL-5F-PINACA.