3,3'',5-Triiodo Thyroacetic Acid (T3-Acetic Acid (USP)) is a thyroid hormone analogue. A potent Thyroxine impurity. Levothyroxine EP Impurity C.
Preparation of 3:5-diiodo-4-(4'-hydroxyphenoxy)phenylacetic acid (diacid): A
solution of ethyl 3:5-diiodo-4-(4'-methoxyphenoxy)phenyl acetate (9.5 g) in
acetic acid (60 ml) was heated under reflux with hydroiodic acid (SG 1.7, 50
ml) and red phosphorus (0.5 g) for 1 hour. The hot solution was filtered and
the filtrate concentrated at 50°C and 15 mm of mercury to above 20 ml. The
residue was treated with water (70 ml) containing a little sodium thiosulfate
to decolorize the product. The solid was collected by filtration and purified by
the method of Harington and Pitt-Rivers [Biochem. J. (1952), Vol. 50, page
438]. Yield 8.36 g (95%). After crystallization from 70% (v/v) acetic acid it
melted at 219°C.
A solution of 438 mg of diac in methanol (20 ml) and ammonia solution (SG
0.88; 20 ml) was iodinated at 0°C with 1.8 ml 1 N iodine solution. The
product was isolated in almost theoretical yield in a manner similar to that
described for tetrac. After crystallization from 50% (v/v) methanol, triac was
obtained as colorless needles which melted over the range 65°C to 90°C
according to the rate of heating. The molten form resolidified at about 110°C
and finally melted at 180°C to 181°C without decomposition. The compound,
dried at 25°C/3 mm over silica gel, contains methanol of crystallization.
