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ABSTRACT: In this report, we disclose our findings regarding the remarkable effect of a low-level impurity found in the solvent used for a ruthenium-catalyzed direct arylation reaction. This discovery allowed for the development of a robust and high-yield arylation protocol that was demonstrated on a multikilogram scale using carboxylate as the cocatalyst. Finally, a practical, scalable, and chromatography-free synthesis of the biaryl core of Anacetrapib is described.
The Journal of Organic Chemistry 02/2011; 76(5):1436-9. · 4.45 Impact Factor
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Carmela Molinaro,
Scott Shultz,
Amélie Roy,
Stephen Lau,
Thao Trinh, Rémy Angelaud,
Paul D O'Shea,
Stefan Abele,
Mark Cameron,
Ed Corley,
Jacques-Alexis Funel,
Dietrich Steinhuebel,
Mark Weisel,
Shane Krska
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ABSTRACT: A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene-ester, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2.
The Journal of Organic Chemistry 01/2011; 76(4):1062-71. · 4.45 Impact Factor
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Carmela Molinaro,
Danny Gauvreau,
Gregory Hughes,
Stephen Lau,
Sophie Lauzon, Rémy Angelaud,
Paul D O'Shea,
Jacob Janey,
Michael Palucki,
Scott R Hoerrner,
Conrad E Raab,
Rick R Sidler,
Michel Belley,
Yongxin Han
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ABSTRACT: A practical large-scale chromatography-free synthesis of EP4 antagonist MF-310, a potential new treatment for chronic inflammation, is presented. The synthetic route provided MF-310 as its sodium salt in 10 steps and 17% overall yield from commercially available pyridine dicarboxylate 7. The key features of this sequence include a unique regioselective reduction of succinimide 2 controlled by the electronic properties of a remote pyridine ring, preparation of cyclopropane carboxylic acid 3 via a Corey-Chaykovsky cyclopropanation, and a short synthesis of sulfonamide 5.
The Journal of Organic Chemistry 09/2009; 74(17):6863-6. · 4.45 Impact Factor
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ABSTRACT: We report herein a simple, scalable, transition-metal-free approach to the synthesis of alpha-aryl methyl ketones from diazonium tetrafluoroborate salts under mild conditions. This methodology uses easily accessible and nontoxic starting material and was applied to the multi-kilogram-scale preparation of 1-(3-bromo-4-methylphenyl)propan-2-one.
The Journal of Organic Chemistry 04/2007; 72(5):1856-8. · 4.45 Impact Factor
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The Journal of Organic Chemistry 04/2005; 70(5):1949-52. · 4.45 Impact Factor
