Crystallization method of Boc-amino acid

Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a crystallization method of Boc amino acid. The preparation method comprises the following steps: (1) reacting free amino acid with di-tert-butyl dicarbonate, carrying out post-treatment to obtain a Boc-protected amino acid reaction solution, and carrying out reduced pressure distillation to remove a solvent until the solvent is dry, thereby obtaining a colorless or light yellow transparent oily substance; (2) adding a seed crystal into the obtained oily substance, standing for a period of time at normal temperature, curing the oily substance to be white, and then adding a weak polar solvent for pulping; (3) pulping for a period of time, filtering, washing, and drying under reduced pressure to obtain the product. According to the method, crystallized Boc amino acid cannot be separated out and crystallized by a conventional method, so that the purity of the product is improved, and meanwhile, the product has certain stability and can be stored for a long time without being decomposed.

Description

technical field

[0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a crystallization method of Boc-amino acid. Background technique

[0002] tert-butoxycarbonyl (Boc) is a widely used amino-protecting group in organic synthesis, especially in peptide synthesis, especially in solid-phase synthesis, Boc is often used for the protection of amino groups. Boc-amino acids have the following advantages:

[0003] 1. Most of Boc-amino acids can be crystallized and can be stored for a long time without decomposition;

[0004] 2. Boc is easy to be removed by acid solution, but has certain stability;

[0005] 3. During the acid hydrolysis of Boc-amino acids, tert-butyl cations are decomposed into isobutene, which generally does not cause side reactions;

[0006] 4. Boc-amino acid is stable to alkali hydrolysis, hydrazinolysis and many nucleophiles;

[0007] 5. Boc-amino acid is stable to catalytic hydrogenolysis.

[0008] Howeve...

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