867309-02-2Relevant academic research and scientific papers
Preparation of a HMG-CoA reductase inhibitor via an optimized imidazole-forming condensation reaction
Bowles, Daniel M.,Bolton, Gary L.,Boyles, David C.,Curran, Timothy T.,Hutchings, Richard H.,Larsen, Scott D.,Miller, Jonathan M.,Park, William K. C.,Ritsema, Kurtis G.,Schineman, David C.,Tamm, Markus
supporting information, p. 1183 - 1187 (2013/01/03)
Development work toward an enabling synthesis of preparative scale batches of an imidazole-based HMG-CoA reductase inhibitor is described. The desired target was synthesized in 16% yield over 7 steps, highlighted by an imidazole-forming condensation reaction in which the yield was improved from 20% to >70% via modification of the solvent, acid, and amine equivalents. The step 2 acylation was improved, and a problematic benzyl ester in step 4 was converted into the corresponding benzyl amide to decrease trans-amidation during the step 5 imidazole formation. A highly effective salt formation and crystallization protocol was also developed.
