VERFAHREN ZUR HERSTELLUNG VON NATRIUM-1-THYROXIN DURCH OXIDATIVE KUPPLUNG VON DIIODO-L-THYROSINE, KATALYSIERT DURCH EIN MANGAN-SALZ UND IN GEGENWART EINES AMINES

摘要

PCT No. PCT/EP95/04017 Sec. 371 Date Apr. 7, 1997 Sec. 102(e) Date Apr. 7, 1997 PCT Filed Oct. 12, 1995 PCT Pub. No. WO96/11904 PCT Pub. Date Apr. 25, 1996Improvements to a six stage process for production of sodium l-thyroxine from l-tyrosine [described in U.S. Pat. No. 2,889,363 and U.S. Pat. No. 2,889,364 (Baxter)] are described, the improvements comprising the oxidative coupling of a diiodo-l-thyrosine to form a biphenyl ether derivative, catalysed by a manganese salt in which the amine and acid functionally of the diiodo-l-thyrosine have been protected by suitable protecting groups, characterised in that the reaction is performed at a pressure of about 20 atmospheres in the presence of an organic amine additive using a gaseous oxidant comprising oxygen and optionally an inert diluent. The process optionally further comprises acid hydrolysis of the biphenyl ether derivative with hydrochloric acid to form a l-thyroxine hydrochloride salt and generation of sodium-l-thyroxine from the l-thyroxine hydrochloride salt.