BG62727B1 - Method for the preparation of ferrous-bis-dl-aspartate - Google Patents

Abstract

The method can be used in the pharmaceutical industry. It achieves a high yield over 96%, reduces the time of the technological process, reduces the quantity of the waste products and turns out pure product which without any additional purification can be introduced in pharmaceutical forms. The method consists in direct reaction between DL-asparginic acid and powder iron in water medium, with boiling in nitrogen atmosphere. 1 claim, 1 figure

Description

Technical field

The invention relates to the preparation of an aspartic acid ferric salt which can be used in the pharmaceutical industry, in particular for the preparation of anti-anemic agents.

BACKGROUND OF THE INVENTION

There is a known method for the preparation of ferric salts of aspartic acid-monolayer aspartate and neutral ferrous aspartate [UK patent 910 321]. The method consists of reacting aspartic acid with an iron or ferric salt, such as carbonate, in an aqueous medium, in the absence of oxygen, or in an inert or reducing atmosphere. The process can be carried out in an open container, but under a protective layer of an organic solvent such as toluene. The preparation of mono-iron aspartate is carried out, for example, by refluxing aspartic acid dissolved in water (1 g mol) in the presence of iron powder (0.6 g atom) in a nitrogen or carbon dioxide atmosphere for 3 to 4 hours. The resulting slurry containing excess iron was filtered to isolate the access to air, the filtrate was collected under a layer of toluene 1 cm thick. The resulting iron aspartate solution was cooled to 0 ° C with stirring. The crystals were air-dried, washed with boiling water, then with ethanol and dried at 100 ° C under reduced pressure. The mono-iron aspartate obtained is a pale green crystalline product, highly soluble in water, insoluble in alcohol, acetone and aromatic solvents. It decomposes above 200 ° C without melting.

SUMMARY OF THE INVENTION AND ADVANTAGES

The process for the preparation of iron-bisDL-aspartate according to the invention is carried out by initially reacting DL-aspartic acid with powdered iron in an aqueous medium at reflux for about 4 hours under nitrogen atmosphere, after which the excess is filtered by iron. The reaction mixture was cooled to 0-5 ° C and centrifuged in a nitrogen atmosphere. In the next interaction, the separated mother liquors from the previous process are used as the medium. The use of the mother liquors as the medium results in a reduction of the losses of the desired P1 ⁺ salt contained therein.

Although the Fe ²⁺ -con contained in the mother liquors is oxidized to some extent to Fe ~ -con, this does not affect the efficiency of the process, since upon re-interaction, the separated averaged hydrogen recovers the iron-bis-DLaspartate and also inhibits oxidation, which eliminates the need for an inert atmosphere.

The advantages of the process according to the invention are as follows. A quantitative yield (over 96%) of a chromatographically purified product is obtained, which without further purification operations can be applied in pharmaceutical forms. The quantity of waste products is reduced, the technological process is simplified and the time for its carrying out is shortened.

An exemplary embodiment of the invention

Example 1. Preparation of iron-bisDL-acnapTaT.4 H2O

To 450 l of distilled and deaerated water, heated to 6O-7O ° C, 133.1 kg (1 kmol) of DL-aspartic acid and 33.4 (0.5881 kmol) of iron powder were added sequentially. The reaction mixture was refluxed under nitrogen for 4 hours, then the heating was stopped, the reaction mixture was filtered on a filter press and the filtrate was cooled to 0-5 ° C in vacuo, and crystallizes iron-bis-DLaspartate. The crystallization mass was stirred for 3 hours at the same temperature, after which the precipitate was centrifuged, maintaining the inert atmosphere and washing several times with ethanol (ca. 301). The crystals separated after drying were 160 kg (81.6%). 133.1 kg of DL-aspartic acid and 33.4 kg of iron powder were added to the separated mother liquors. After carrying out the reaction and subsequent operations in the manner described above, a product of 190 kg (96.9%) was obtained. The whole procedure was repeated 4 more times to give a product with a total mass of 1100 kg (93.5%), chromatographically purified on an ethanol system (95%): NH3 (25%). 55:15.

Elemental analysis: Empirical formula C ₈ H ₁₂ N ₂ O ₈ Fe.4H ₂ O

Calculated, in%: Fe 14.24, C 24.5, H 5.1, N 7.14

Found in%: Fe 14.29, C 24.33, H 5.18, N 7.03.

In the accompanying FIG. 1 shows an IR spectrogram of the compound obtained.

Claims (1)

Claims 1. A process for the preparation of iron-bisDL-aspartate by reaction of DL-acaragic acid and iron powder, characterized in that the interaction of DL-aspartic acid and iron powder is initially carried out in aqueous medium at reflux for 5 about 4 h in nitrogen atmosphere, then filtered excess iron, cooled the reaction mixture to 0-5 ° C and centrifuged in nitrogen atmosphere, using the following medium as the medium using 10 wt. mother liquors from the previous implementation. process. Attachment: 1 figure Literature 1. GB 910321. Publication of the Patent Office of the Republic of Bulgaria 1113 Sofia, 52-B Dr. GM Dimitrov Blvd. Expert: L. Tsingileva Editor: V. Altavanov Cf. № 40119 Circulation: 40 MB