Development of a large scale asymmetric synthesis of the glucocorticoid agonist BI 653048 BS H3PO4

…, A Chitroda, P DeCroos, T Fachinger…

文献索引：Reeves, Jonathan T.; Fandrick, Daniel R.; Tan, Zhulin; Song, Jinhua J.; Rodriguez, Sonia; Qu, Bo; Kim, Soojin; Niemeier, Oliver; Li, Zhibin; Byrne, Denis; Campbell, Scot; Chitroda, Ashish; Decroos, Phil; Fachinger, Thomas; Fuchs, Victor; Gonnella, Nina C.; Grinberg, Nelu; Haddad, Nizar; Jaeger, Burkhard; Lee, Heewon; Lorenz, Jon C.; Ma, Shengli; Narayanan, Bikshandarkoil A.; Nummy, Larry J.; Premasiri, Ajith; Roschangar, Frank; Sarvestani, Max; Shen, Sherry; Spinelli, Earl; Sun, Xiufeng; Varsolona, Richard J.; Yee, Nathan; Brenner, Michael; Senanayake, Chris H. Journal of Organic Chemistry, 2013 ,  vol. 78,  # 8  p. 3616 - 3635

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被引用次数: 27

摘要

The development of a large scale synthesis of the glucocorticoid agonist BI 653048 BS H3PO4 (1· H 3 PO 4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl) ethyl amide was prepared by an enolization/bromine–magnesium exchange/electrophile trapping reaction. A nonselective propargylation of trifluoromethyl ketone 22 gave the desired diastereomer in 32% yield and with dr= 98: 2 from a 1: 1 ...