An Unusual Trifluoromethyl Elimination Reaction from the 4,4-Bis(trifluoromethyl)-5-hydroxyimidazoline Ring System.
A facile detrifluoromethylation was observed when 4,4-bis(trifluoromethyl)-5-hydroxyimidazoline 5 was treated with a variety of bases to afford the biologically interesting 4-(trifluoromethyl)imidazole analogs (9 and 10). A unique mechanism was proposed for this transformation, supported by isolating and trapping the hypothesized intermediates. Heating of 5 with Et(4)NCN in DMSO provided 19, which was clearly derived from the proposed intermediate 17. Finally, imidazole 9 was converted into the N-[2-phenyl-4-(trifluoromethyl)-1H-imidazol-5-yl]-N-methylbenzamide analogs, which were potential acyl CoA:cholesterol acyltransferase (ACAT) inhibitors.
Li
Hui-Yin
HY
The DuPont Merck Pharmaceutical Company, Chemical Sciences Division, Experimental Station, Wilmington, Delaware 19880-0500, and The DuPont Merck Pharmaceutical Company, Chemical Process R&D, Chambers Works, Deepwater, New Jersey 08023-0999.
DeLucca
Indawati
I
Drummond
Spencer
S
Boswell
George A.
GA