Hydrochloric Acid → N-Acetylthyroxine

Participants

Reaction Steps

L-Thyroxine sodium salt, pentahydrate (1) (10 g, 11 mmol) was nearly completely dissolved in 400 mL of EtOH/2N NH4OH (1/1, v/v), filtered, and filtrate poured into 425 mL of 5% HCl. The resulting precipitate was isolated by vacuum filtration and dried under high vacuum to afford a white solid. This material was dissolved in 160 mL DMF, 100 mL (1.06 mol) of acetic anhydride added, and reaction stirred for 1.5 hours, then diluted with 850 mL H2O and allowed to stand at 4° C. for 16 hours. The resulting precipitate was isolated by filtration, then dissolved in 350 mL EtOH and 41 mL of 1N NaOH, stirred for 2.5 hours, 680 mL of 5% HCl added, and mixture allowed to stand at 4° C. for 16 hours. The resulting precipitate was isolated by vacuum filtration and dried under high vacuum to yield 8.1 g (90%) of the desired N-acetyl L-thyroxine (5) as a white solid; 1H NMR (200 MHz, CD3OD) d 7.8 (s, 2H), 7.1 (s, 2H), 4.6-4.7 (m, 1H), 2.8-3.0 (m, 2H), 2.0 (s, 3H); mass spec (FAB) (M+H)+ 820.

Provenance & Evidence