A scalable process for the novel antidepressant ABT-200

被引：23

作者：

Deshpande, MN ^{[1
]}

Cain, MH ^{[1
]}

Patel, SR ^{[1
]}

Singam, PR ^{[1
]}

Brown, D ^{[1
]}

Gupta, A ^{[1
]}

Barkalow, J ^{[1
]}

Callen, G ^{[1
]}

Patel, K ^{[1
]}

Koops, R ^{[1
]}

Chorghade, M ^{[1
]}

Foote, H ^{[1
]}

Pariza, R ^{[1
]}

机构：

[1] Abbott Labs, Proc Res & Dev, N Chicago, IL 60064 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 1998年 / 2卷 / 06期

关键词：

D O I：

10.1021/op9800414

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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.

引用

页码：351 / 356

页数：6

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