- Preparation method of levothyroxine sodium
-
The invention belongs to the field of pharmaceutical synthesis, and discloses a preparation method of levothyroxine sodium. The preparation method comprises the following steps: (1) taking 3,5-diiodo-L-tyrosine as a raw material, and preparing N-acetyl-L-tyrosine by firstly introducing acetyl protection to an amino group; (2) then preparing N-acetyl-3,5-diiodo-L-tyrosine ethyl ester under the action of thionyl chloride; (3) preparing N-acetyl-O-(4-methyoxyphenyl)-3,3-diiodo-L-tyrosine ethyl ester by carrying out Chan-Lam reaction through copper catalysis; (4) removing a protective group undera strong acidity condition, thus obtaining O-(4-hydroxyphenyl)-3,5-diiodo-L-tyrosine; (5) then reacting with iodine, and preparing O-(4-hydroxy-3,5-diiodo phenyl)-3,5-diiodo-L-tyrosine disodium salt under the action of sodium hydroxide; (6) finally, regulating pH (Potential of Hydrogen) through glacial acetic acid, thus obtaining the levothyroxine sodium. According to the preparation method disclosed by the invention, the key Chan-Lam reaction and other reaction steps are optimized, so that the reaction time can be greatly shortened, and the reaction yield can be increased; the preparation method is simple in technology, convenient to operate and suitable for industrial production.
- -
-
Paragraph 0009; 0032; 0033
(2019/06/05)
-
- Synthesis of diaryl ethers through the copper-promoted arylation of phenols with arylboronic acids. An expedient synthesis of thyroxine
-
Diaryl ethers are readily synthesized in high yield at room temperature through the copper(II)-promoted coupling of arylboronic acids and phenols. The reaction is tolerant of a wide range of substituents on both coupling partners. These reaction condition
- Evans, David A.,Katz, Jeffrey L.,West, Theodore R.
-
p. 2937 - 2940
(2007/10/03)
-