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

Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

The Journal of organic chemistry 2001 Jun 29

filter terms:

We demonstrate that "FBr" addition to 1-trityl-4-vinyl-1H-imidazole (7) provides a convenient route to side-chain-fluorinated histamines. Thus, addition of "FBr" to the double bond of 7 occurs with Markovnikov regioselectivity to produce 4-(2-bromo-1-fluoroethyl)-1-trityl-1H-imidazole (8). Substitution with azide, reduction, and removal of the trityl group provide beta-fluorohistamine (1) as the dihydrochloride. Elimination of HBr from 8 followed by a second addition of "FBr" gives 4-(2-bromo-1,1-difluoroethyl)-1-trityl-1H-imidazole (15). This was similarly converted to beta,beta-difluorohistamine (2) as the dihydrochloride.

Citation

B Dolensky, K L Kirk. New building blocks for fluorinated imidazole derivatives: preparation of beta-fluoro- and beta,beta-difluorohistamine. The Journal of organic chemistry. 2001 Jun 29;66(13):4687-91