Preparation of a HMG-CoA Reductase Inhibitor via an Optimized Imidazole-Forming Condensation Reaction

Autor:	Daniel Merritt Bowles, David C. Schineman, Markus Tamm, Kurtis G. Ritsema, Jonathan Mark Miller, William Keun Chan Park, David C. Boyles, Scott D. Larsen, Richard H. Hutchings, Timothy T. Curran, Gary Louis Bolton
Rok vydání:	2008
Předmět:	Acylation Solvent chemistry.chemical_compound Chemistry Amide Yield (chemistry) Organic Chemistry Imidazole Organic chemistry Amine gas treating Physical and Theoretical Chemistry Reductase Condensation reaction
Zdroj:	Organic Process Research & Development. 12:1183-1187
ISSN:	1520-586X 1083-6160
Popis:	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.
Databáze:	OpenAIRE
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