Process Research and Development of TP-808: A Key Intermediate for the Manufacture of Synthetic Tetracyclines

Process research, development, and manufacture of TP-808 (1), a key intermediate for the discovery and manufacture of tetracycline analogues, is described. The process used for the preparation of 1 avoids chromatographic purifications and has been substantially improved over the previously reported preparation. The robustness of the process was demonstrated in a 76.1 kg manufacturing campaign with 56% overall yield.