New building blocks for fluorinated imidazole derivatives: Preparation of beta-fluoro- and beta,beta-difluorohistamine

We demonstrate that "FBr" addition to 1-trityl-4-vinyl-1H-imidazole (7) pro vides a convenient route to side-chain-fluorinated histamines. Thus, additi on of "FBr" to the double bond of 7 occurs with Markovnikov regioselectivit y to produce 4-(2-bromo-1-fluoroethyl)-1-trityl-1H-imidazole (8). Substitut ion with azide, reduction, and removal of the trityl group provide beta -fl uorohistamine (1) as the dihydrochloride. Elimination of HBr from 8 followe d by a second addition of "FBr" gives 4-(2-bromo-1,1-difluoroethyl)-1-trity l-1H-imidazole (15). This was similarly converted to beta,beta -difluorohis tamine (2) as the dihydrochloride.