Process for producing S-tetrahydrochysene furoic acid

Abstract

The invention discloses a method for preparing S-tetrahydrofurfuryl acid. The method comprises the following steps: using R-phenethylamine and racemic tetrahydrofurfuryl acid to obtain tetrahydrofurfuryl acid phenethylamine salt, and obtaining pure diastereoisomer salt after the tetrahydrofurfuryl acid phenethylamine salt is refined; after ammonia gas is introduced into the salt, obtaining tetrahydrofurfuryl acid ammonia salt, and reclaiming phenethylamine; and adjusting pH value of the tetrahydrofurfuryl acid ammonia salt to be acidic, extracting free tetrahydrofurfuryl acid by using a continuous extraction method, and decompressing and distilling the free tetrahydrofurfuryl acid to obtain the optically pure finished product of the S-tetrahydrofurfuryl acid. Moreover, a by-product containing the R-tetrahydrofurfuryl acid, which is generated after separated mother liquor is dissociated by the ammonia gas, is racemized by alkali to obtain the racemic tetrahydrofurfuryl acid which can be used as a raw material for reutilization. The method has the advantages of low cost and high purity of the product, and is suitable for industrialized production.

Description

technical field [0001] The present invention relates to the preparation of chiral drugs. In particular, it relates to a preparation method of optically pure S-tetrahydrofuroic acid, a chiral drug intermediate. Background technique [0002] S-tetrahydrofuroic acid is a key intermediate of many chiral drugs, such as the antihypertensive drug terazosin, which uses S-tetrahydrofuroic acid as an important intermediate. Usually mixed tetrahydrofuroic acid can be easily synthesized from furfural, but because the resolution of tetrahydrofuroic acid is relatively difficult, and in addition, due to the high water solubility of tetrahydrofuroic acid, the separation is relatively difficult, so the yield is relatively low. [0003] Can.J.Chem.61, 13836, 1983 first reported a kind of resolution method, what used is that toxicity is very big, and relatively expensive strychnine is used as resolution agent, resolution yield and resolution agent recovery rate Not high either. Chinese pate...

AI Technical Summary

Problems solved by technology

And this resolving agent needs to be prepared by the user, and the raw material is a by-product of the synthesis of chloramphenicol, so it is difficult to purchase commercially

Chem.Eur.J.4, 1621, 1998 reported the method of using dibenzoyltartaric acid as a resolving agent, although the yield is better, a lot of calcium oxide will be used, and the three wastes problem is serious

In addition, JP01216983, 1989, EP382506, 1990, US4985575, 1991, reported the use of optically active amines of the α-methylbenzylamine type as a resolving agent. The solvent and conditions are relatively high, and it takes multiple recrystallizations to achieve a high e.e. value. At the same time, the loss in the process of dissociation and extraction is large, and the amount of solvent used is large, and most of the vortex is discarded during the split. Hydrofuric acid raw material, so the cost is higher