- Preparation method of levothyroxine sodium
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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.
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Paragraph 0009; 0028; 0029
(2019/06/05)
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- Facile syntheses of 3-halo and mixed 3,5-dihalo analogues of N-acetyl-l-tyrosine via sulfonic acid-catalysed regioselective monohalogenation
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The combination of catalytic amounts of p-toluenesulfonic acid and 1 equiv of N-halosuccinimide afforded highly selective ring-halogenation of N-acetyl-l-tyrosine, furnishing either N-acetyl-3-halo-l-tyrosine analogues or mixed 3,5-dihalo derivatives in a one-pot reaction with excellent yields at room temperature.
- Bovonsombat, Pakorn,Khanthapura, Pratheep,Krause, Michael M.,Leykajarakul, Juthamard
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body text
p. 7008 - 7011
(2009/04/10)
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