- An improved manufacturing process for the antimalaria drug coartem. Part II
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The manufacturing process for lumefantrine, 2, one of the two active principles in the fixed-dose combination of the anti-malarial drug Coartem, was reworked. For the conversion of 2-chloro-1-(2,7-dichloro-9H-fluoren-4-yl) ethanone, 5, to 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol, 8, a onepot process was developed that eliminated isolation of the epoxide 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane, 7. Significant increase in throughput was achieved by applying new reaction and crystallization conditions for the Knoevenagel condensation of 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl) ethanol, 8, to 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(Z)- ylidene]-9H-fluoren-4-yl}ethanol, 2.
- Beutler, Ulrich,Fuenfschilling, Peter C.,Steinkemper, Andreas
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p. 341 - 345
(2012/12/31)
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