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Synfacts 2011(6): 0579-0579  
DOI: 10.1055/s-0030-1259889
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of the Biaryl Core of Anacetrapib

Contributor(s): Philip Kocienski
S. G. Ouellet*, A. Roy, C. Molinaro, R. Angelaud, J.-F. Marcoux, P. D. O’Shea, I. W. Davies
Merck Frost Canada, Kirkland, Canada and Merck & Company, Rahway, USA
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Publikationsdatum:
19. Mai 2011 (online)

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Significance

Anacetrapib inhibits cholesteryl ester transfer protein (CETP), a plasma glycoprotein that transfers cholesteryl ester from high density ­lipoprotein to low density lipoprotein and very low density lipoprotein, consequently lowering the risk of atherosclerosis. Key steps in the synthesis depicted are (1) a highly regioselective SNAr reaction of 1-bromo-2,4-fluorobenzene (A) with potassium methoxide (rr =17:1) and (2) a multi-kilogram scale ruthenium-catalyzed direct arylation of oxazoline F to construct the biaryl G.