A Scalable Process for the Novel Antidepressant ABT-200
A scalable process for the novel antidepressant ABT-200, starting with 5,6-methylenedioxy-1-tetralone, is described. The new process improves the scale-up and safety concerns associated with the previously employed route to ABT-200. The scalable process eliminates the potential for HCN exposure to e...
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| Veröffentlicht in: | Organic process research & development 1998-11, Vol.2 (6), p.351-356 |
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| creator | Deshpande, Mahendra N Cain, Michael H Patel, Subhash R Singam, Pulla Reddy Brown, David Gupta, Ashok Barkalow, Jufang Callen, Gary Patel, Ketan Koops, Roger Chorghade, Mukund Foote, Howard Pariza, Richard |
| description | A scalable process for the novel antidepressant ABT-200, starting with 5,6-methylenedioxy-1-tetralone, is described. The new process improves the scale-up and safety concerns associated with the previously employed route to ABT-200. The scalable process eliminates the potential for HCN exposure to employees and produces ABT-200 in a stereospecific fashion. (TMS)CN was replaced by nitromethane as a reagent to introduce the nitrogen in the ABT-200 molecule. This stereospecific process employs an epimerization procedure which takes advantage of a key difference in the solubility of the two diastereomers of the succinimide intermediate, 9a/b and 10a/b. Balancing the rate of epimerization with the solubility of the diastereomers in the reaction medium was an essential factor in optimizing the yield and efficiency of this simple, one-pot reaction. The solubility-directed epimerization was demonstrated in both a predominantly aqueous and an organic solvent mixture. The succinimide derivative 10a/b was then converted to ABT-200. This improved procedure was used to prepare kilogram quantities of ABT-200. |
| doi_str_mv | 10.1021/op9800414 |
| format | Article |
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Process Res. Dev</addtitle><description>A scalable process for the novel antidepressant ABT-200, starting with 5,6-methylenedioxy-1-tetralone, is described. The new process improves the scale-up and safety concerns associated with the previously employed route to ABT-200. The scalable process eliminates the potential for HCN exposure to employees and produces ABT-200 in a stereospecific fashion. (TMS)CN was replaced by nitromethane as a reagent to introduce the nitrogen in the ABT-200 molecule. This stereospecific process employs an epimerization procedure which takes advantage of a key difference in the solubility of the two diastereomers of the succinimide intermediate, 9a/b and 10a/b. Balancing the rate of epimerization with the solubility of the diastereomers in the reaction medium was an essential factor in optimizing the yield and efficiency of this simple, one-pot reaction. 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Process Res. Dev</addtitle><date>1998-11-01</date><risdate>1998</risdate><volume>2</volume><issue>6</issue><spage>351</spage><epage>356</epage><pages>351-356</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>A scalable process for the novel antidepressant ABT-200, starting with 5,6-methylenedioxy-1-tetralone, is described. The new process improves the scale-up and safety concerns associated with the previously employed route to ABT-200. The scalable process eliminates the potential for HCN exposure to employees and produces ABT-200 in a stereospecific fashion. (TMS)CN was replaced by nitromethane as a reagent to introduce the nitrogen in the ABT-200 molecule. This stereospecific process employs an epimerization procedure which takes advantage of a key difference in the solubility of the two diastereomers of the succinimide intermediate, 9a/b and 10a/b. Balancing the rate of epimerization with the solubility of the diastereomers in the reaction medium was an essential factor in optimizing the yield and efficiency of this simple, one-pot reaction. The solubility-directed epimerization was demonstrated in both a predominantly aqueous and an organic solvent mixture. The succinimide derivative 10a/b was then converted to ABT-200. This improved procedure was used to prepare kilogram quantities of ABT-200.</abstract><pub>American Chemical Society</pub><doi>10.1021/op9800414</doi><tpages>6</tpages></addata></record> |
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| ispartof | Organic process research & development, 1998-11, Vol.2 (6), p.351-356 |
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| source | ACS Publications |
| title | A Scalable Process for the Novel Antidepressant ABT-200 |
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