Enantioselective Synthesis of a Highly Substituted Tetrahydrofluorene Derivative as a Potent and Selective Estrogen Receptor Beta Agonist

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• 作者：Matthew L. Maddess ; Jeremy P. Scott ; Anthony Alorati ; Carl Baxter ; Nadine Bremeyer ; Sarah Brewer ; Kevin Campos ; Ed Cleator ; Alejandro Dieguez-Vazquez ; Andrew Gibb ; Andrew Gibson ; Melissa Howard ; Stephen Keen ; Artis Klapars ; Jaemoon Lee ; Jing Li ; Joseph Lynch ; Peter Mullens ; Debra Wallace ; Robert Wilson
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：April 18, 2014
• 年：2014
• 卷：18
• 期：4
• 页码：528-538
• 全文大小：590K
• 年卷期：v.18,no.4(April 18, 2014)
• ISSN：1520-586X

文摘

The development and execution of a practical asymmetric synthesis of the estrogen receptor beta selective agonist (8R,10aS)-6-(trifluoromethyl)-8,9,10,11-tetrahydro-8,10a-methanocyclohepta[1,2]indeno[4,5-d][1,2,3]triazol-7(3H)-one is described. The optimized route features a key chiral auxiliary-mediated dialkylation approach to set the all-carbon quaternary center with exceptional stereocontrol. Overall, the chemistry has been used to prepare >30 kg of drug candidate in 21% overall yield through 13 longest linear steps and with >99% ee.