A Scalable Process for the Novel Antidepressant ABT-200

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• 作者：Mahendra N. Deshpande ; Michael H. Cain ; Subhash R. Patel ; Pulla Reddy Singam ; David Brown ; Ashok Gupta ; Jufang Barkalow ; Gary Callen ; Ketan Patel ; Roger Koops ; Mukund Chorghade ; Howard Foote ; and Rich
• 刊名：Organic Process Research & Development
• 出版年：1998
• 出版时间：November 1998
• 年：1998
• 卷：2
• 期：6
• 页码：351 - 356
• 全文大小：97K
• 年卷期：v.2,no.6(November 1998)
• ISSN：1520-586X

文摘

A scalable process for the novel antidepressant ABT-200,starting with 5,6-methylenedioxy-1-tetralone, is described. Thenew process improves the scale-up and safety concerns associated with the previously employed route to ABT-200. Thescalable process eliminates the potential for HCN exposure toemployees and produces ABT-200 in a stereospecific fashion.(TMS)CN was replaced by nitromethane as a reagent tointroduce the nitrogen in the ABT-200 molecule. This stereospecific process employs an epimerization procedure whichtakes advantage of a key difference in the solubility of the twodiastereomers of the succinimide intermediate, 9a/b and 10a/b. Balancing the rate of epimerization with the solubility ofthe diastereomers in the reaction medium was an essential factorin optimizing the yield and efficiency of this simple, one-potreaction. The solubility-directed epimerization was demonstrated in both a predominantly aqueous and an organic solventmixture. The succinimide derivative 10a/b was then convertedto ABT-200. This improved procedure was used to preparekilogram quantities of ABT-200.