3-phenylisoserine derivative production method

Abstract

The present invention provides a 3-phenylisoserine derivative production method for obtaining 3-phenylisoserine derivatives represented by formula (2) (in the formula, R1 represents a phenyl group or a phenyl group having a substituent group; R3 represents a hydrogen atom, a methyl group, a benzyl group, a p-methoxybenzyl group, a tert-butly group, a methoxymethyl group, a 2-tetrahydropyranyl group, an ethoxyethyl group, an acetyl group, a pivoloyl group, a benzoyl group, a trimethylsilyl group, a triethylsilyl group, or a tert-butyldimethylsilyl group; R4 represents a formyl group, an acetyl group, a benzoyl group, a tert-butoxycarbonyl group, or a benzyloxycarbonyl group; and R5 represents a C1-4 alkyl group) by protecting, in water or a mixed solvent containing water, the amino group of a compound represented by formula (1) (in the formula, R1 represents a phenyl group or a phenyl group having a substituent group; R2 represents an alkali metal, an alkaline earth metal, or a nitrogenous base; and R3 represents a hydrogen atom, a methly group, a benzyl group, a p-methoxybenzyl group, a tert-butyl group, a methoxymethyl group, a 2-tetrahydropyranyl group, an ethoxymethly group, an acetyl group, a pivoloyl group, a benzoyl group, a trimethylsilyl group, a triethylsilyl group, or a tert-butyldimethylsilyl group), and when a specific compound has been obtained, extracting the compound using a C4 ether solvent, and while removing the C4 ether solvent and moisture content, replacing at least some of the C4 ether solvent with a C1-4 aliphatic alcohol and implementing an esterification reaction, and then isolating the 3-phenylisoserine derivative at 0-30 DEG C. The 3-phenylisoserine derivative production method enables the production of 3-phenylisoserine derivatives having at least 99% purity.

Description

technical field [0001] The present invention relates to a method for producing 3-phenylisoserine derivatives important as raw materials for pharmaceutical intermediates and the like. Background technique [0002] Compounds having a β-amino acid moiety, such as 3-phenylisoserine derivatives, are known as compounds useful in industries such as medicine. As a method for producing a 3-phenylisoserine derivative, for example, the following method is known. [0003] (1) In the presence of boron trifluoride, methyl phenyl glycidate is subjected to a ring-opening reaction with azide, and the obtained azide is subjected to benzoylation and catalytic hydrogenation to produce N-benzoyl - the method of 3-phenylisoserine methyl ester (refer to Patent Document 1), [0004] (2) A method of esterifying 3-phenylisoserine in methanol, reacting benzoyl chloride and the concentrate in water to produce N-benzoyl-3-phenylisoserine methyl ester (see Patent Document 2 ), [0005] (3) 3-phenylis...

AI Technical Summary

Problems solved by technology

However, this intermediate has a free amino group and an ester site in the molecule, so in the next reaction to protect the amino group, there is a possibility of by-product intermolecular or intramolecular amides

In addition, in general, the methyl ester body is prone to simultaneous hydrolysis reactions, so the quality is poor and the yield is low

[0008] In the method (3) above, N-benzoyl-3-phenylisoserine ester can be obtained by esterifying crystals isolated by solid-liquid separation. Generally speaking, the crystals precipitated by acid precipitation are very fine. , so solid-liquid separation takes a lot of time, and further, there are problems in industrial production such as high liquid content of crystallization

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