Acetamide → 3,5-Diiodothyronine, L-

Participants

Reaction Steps

Many patent and non-patent literature describe the use of an intermediate called Bis (p-anisyl)iodonium bromide in the preparation of Levothyroxine sodium. Hillmann (Z. Naturforch 1956; 11b:424-425) describes a process for the assembly of the biphenyl-ether system present in Levothyroxine, wherein a key coupling reaction is initiated between N-Acetyl 3,5-diiodo-L-tyrosine ethyl ester, derived from the stepwise protective conversion of amine as amide and acid as ester of 3,5 diido-L-tyrosine, and Bis (p-anisyl)iodonium bromide in the presence of copper metal or powder as a catalyst to afford (S)—N-acetyl-3,5-diiodo-4-p-methoxyphenoxyphenylalanine ethyl ester, with 87% yield. All the three protective groups in (S)—N-acetyl-3,5-diiodo-4-p-methoxyphenoxyphenylalanine ethyl ester, viz. acetamide, methyl ether, ethyl ester were cleaved using a mixture of Hydroiodic acid and Hydrobromic acid to give 3,5-Diiodothyronine. 3,5-Diiodothyronine on subsequent iodination with iodine gave L-thyroxine of an yield that corresponds to 92%.

Provenance & Evidence