PROCESS FOR PRODUCING SODIUM 1-THYROXINE COMPRISING THE OXIDATIVE COUPLING OF A DIIDO-1-TYROSINE CATALYSED BY A MANGANESE SALT IN THE PRESENCE OF AN AMINE

摘要

Improvements to a six-stage process for production of sodium 1-thyroxine from 1-tyrosine ¢described in US 2889363 and US 2889364 (Baxter)! are described, the improvements comprising the oxidative coupling of a diido-1-tyrosine to form a biphenyl ether derivative, catalysed by a manganese salt in which the amine and acid functionality of the diiodo-1-tyrosine 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 1-thyroxine hydrochloride salt and generation of sodium-1-thyroxine from the 1-thyroxine hydrochloride salt.