Li W.,GPRD Process RandD |
Towne T.B.,GPRD Process RandD |
Liang G.,GPRD Process RandD |
Liang G.,Nankai University |
And 2 more authors.
Organic Process Research and Development | Year: 2014
A practical, scalable synthetic process for a sulfonamide was developed featuring a Semmler-Wolff aromatization as the key step. The optimized reaction conditions using HCl in HOAc give directly the desired naphthylamine in high yield as opposed to a naphthylacetamide commonly formed in the Semmler-Wolff reactions. One little known byproduct of anomalous rearrangement, ketoamine, was observed and a mechanism proposed to explain its formation. Employing the optimized process, 360 kg was prepared to support drug development. © 2014 American Chemical Society.