AT403160B - PROCESS FOR THE PREPARATION OF PYRIDOXIN 5-OXO-2-PYRROLIDONE CARBOXYLATE - Google Patents

Description

AT 403 160 B

The present invention relates to a process for the preparation of pyridoxine 5-oxo-2-pyrrolidone carboxylate, which has the following formula:

Pyridoxine 5-oxo-2-pyrrolidone carboxylate is a known substance which has been used for therapeutic purposes for many years.

Pyridoxine, also known as vitamin B6, is a well-known principle of action that has found other uses in the treatment of acute alcoholic intoxications, although certain confusion has arisen regarding its real, positive effects in therapeutic treatments. It was subsequently found, and this is the subject of Italian Patent No. 1,131,856, that the salt of pyridoxine with pyrrolidonecarboxylic acid shows efficient therapeutic effects in the treatment of acute alcoholic intoxications.

Among other symptomatologies that can be treated efficiently with the compound that can be prepared according to the invention, vomiting conditions and those of hyperprolactinias induced by iatrogenic neuroendocrine disorders are also noteworthy.

A simple industrial production of this compound with good yields therefore appears to be important. To date, the preparation of this compound has itself used a process (Italian Patent No. 1,131,855) which involves the reaction under heat and stirring for 30 min of solutions, preferably in ethanol of pyridoxine and pyroglutamic acid, followed by precipitation by cooling the crude reaction product takes advantage of. The latter the latter was then subjected to purification by chromatography on an ion exchange resin, finally isolating the desired product by precipitating the residue obtained by evaporation under reduced pressure of the eluate.

The main object of the present invention is to provide a process for the production of the main product which should prove to be industrially advantageous in terms of both the yield point of view and the simple production process.

For this purpose, the present invention provides a process for the preparation of pyridoxine 5-oxo-2-pyrrolidone carboxylate, which has the following formula:

2nd

AT 403 160 B is available, which is characterized in that equimolecular amounts of pyridoxine base and pyroglutamic acid are reacted as solid powders, which are mixed thoroughly and mixed with a small amount of 5-10% deionized water containing isopropanol.

The product, which slowly forms in the crystalline state, is granulated, dried and finally crystallized from warm isopropanol.

The salt form obtained therefrom is confirmed by the melting point and by the I.R. spectrum, which shows characteristic absorption bands of the salt which are different from those of the two starting products.

The DSC spectrum confirms the formation of the desired salt.

The salt obtained has a molecular weight of 298.28 and the following composition in percent: C: 52%, H: 6.08%, N: 9.33% and 0: 32.18% and has the appearance of a white, odorless , crystalline powder, which has a melting point of 96 to 98 ° C and which has a slightly acid taste, is highly water-soluble, is poorly soluble in cold ethanol and is insoluble in conventional organic solvents such as acetone, ethyl ester, chloroform and benzene.

From the foregoing description, as well as from the illustrative example that follows, it will be clearly understood that the method according to the present invention achieves the purposes set out above and therefore has a high level of industrial interest.

EXAMPLE 8.663 kg of 1,2-pyrrolidone-5-carboxylic acid and 1.337 kg of pyridoxine base are carefully sieved and mixed for 30 minutes.

9 l of a solution of isopropanol containing 400 ml of deionized water are added to the resulting mixture, the solution being kept at 35 ° C.

After stirring for 10 minutes, a paste is obtained, which are slowly solidified.

The crystalline mass resulting from this is granulated and dried in vacuo at 38 * C for 24 hours.

The resulting solid (18.6 kg, 93% yield) is dissolved in about 40 l of boiling isopropanol, allowed to crystallize at 40 ° C. and finally filtered and dried at 38 ° C. for a further 24 hours, which gives the following analytical data :

Melting point: 98-100 “C NMR: (in D20) as in FIG. 1 DSC: as in FIG. 2 IR: as in FIG. 3 TABLE 2

Analysis parameters

Initial temperature * C 60 variation K / min 10 final temperature * C 160 ISO time min 0 diagram cm 10 FS range mW 20 fluctuations% 90 types of plates 1/2 2 mW limit 0 sieve DYN / ISO 1/2 0 identification number 1 Weight in mg 5.4

The above example is obviously primarily illustrative and not restrictive, so that changes and variations that are conceptually equivalent are possible and predictable 3

Claims (3)

AT 403 160 B still remain within the limits of this invention. 1. Process for the preparation of pyridoxine 5-oxo-2-pyrrolidone carboxylate, which has the following formula: CH2OH CH3 ---- \ + / N 1 H, characterized in that equimolecular amounts of pyridoxine base and pyroglutamic acid are reacted as solid powders, which are carefully mixed and mixed with a small amount of 5-10% deionized water containing isopropanol. 2. The method according to claim 1, characterized in that the reaction product in the form of a paste is allowed to stand until a crystalline solid is formed, which is granulated and vacuum-dried under heat. 3. The method according to claim 1, characterized in that the cleaning is carried out by crystallization from isopropanol. Including 3 sheets of drawings 4