Phillip Hopes, Andrew Parker, I. Patel
May 19, 2006
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0
Influential Citations
17
Citations
Journal
Organic Process Research & Development
Abstract
(S)-3-(5-Oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinolin-4-yl)benzonitrile is a potassium-channel opener developed for the treatment of urinary urge incontinence. The key step in the synthesis is an unsymmetrical Hantzsch reaction to give a 2-hydroxy-1,2,3,4-tetrahydropyridine. In our study the order of addition of reagents was found to be critical in the optimisation of the yield and the control of impurity levels in this reaction. The yield and the relative charges of the reagents were further optimised by the use of factorial experimental design. The chemistry has been scaled up to plant scale to produce multikilogram amounts of the Hantzsch product in close to 60% yield.