New polymorph and new path to synthesize tafamidis

A process for the production of 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid (2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol F (Tafemidis meglumine) comprising the step of cyclization of 4-(3,5-dichlorobenzamido)-3-hydroxybenzoic acid D in the presence of acetic acid and a sulfonic acd to yield the Tafamidis acetic acid adduct E followed by adduct exchange with N-Methyl-D-Glucamine; precipitation and drying of the precipitate to give Tafamidis meglumine. The process is preferably conducted in glacial acetic acid, and the sulfonic acid is preferably p-toluenesulfonic acid. The temperature of the process is preferably below 125°C. The process preferably comprises the additional step of contacting the obtained Tafamidis meglumine with an aprotic solvent with successive removal of the solvent to yield crystalline Tafamidis meglumine. A crystalline form of Tafamidis meglumine is also disclosed characterized by powder X-ray diffraction peaks at 12.2, 23.0 and 25.5 (2θ ± 0.2; which may further comprise peaks at 5.5, 17.2 and 24.7. Pharmaceutical compositions comprising the crystalline form are disclosed, and their use in the treatment of familial amyloid polyneuropathy (FAP), familial transthyretin (TTR) amyloidosis or transthyretin familial amyloid polyneuropathy.