A Practical Enantioselective Synthesis of Odanacatib, a Potent Cathepsin K Inhibitor, via Triflate Displacement of an α-Trifluoromethylbenzyl Triflate

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• 作者：Paul D. O’ ; Shea*^† ; ; Cheng-yi Chen^‡ ; ; Danny Gauvreau^† ; ; Francis Gosselin^† ; ; Greg Hughes^† ; ; Christian Nadeau^R
• 刊名：Journal of Organic Chemistry
• 出版年：2009
• 出版时间：February 20, 2009
• 年：2009
• 卷：74
• 期：4
• 页码：1605-1610
• 全文大小：187K
• 年卷期：v.74,no.4(February 20, 2009)
• ISSN：1520-6904

文摘

An enantioselective synthesis of the Cathepsin K inhibitor odanacatib (MK-0822) 1 is described. The key step involves the novel stereospecific S_N2 triflate displacement of a chiral α-trifluoromethylbenzyl triflate 9a with (S)-γ-fluoroleucine ethyl ester 3 to generate the required α-trifluoromethylbenzyl amino stereocenter. The triflate displacement is achieved in high yield (95%) and minimal loss of stereochemistry. The overall synthesis of 1 is completed in 6 steps in 61% overall yield.