CS239428B1 - Syn-form of anhydrous 2-methoxyimino-2- (2-amino-1,3-thiazol-4-yl) acetic acid and process for its preparation - Google Patents

Abstract

Syn-form of anhydrous 2-methoxyimino-2-?2-amino-1,3-thiazol-4-yl/acetic acid, a new substance, useful as a very advantageous intermediate in the synthesis of aminothiazole beta-lactam antibiotics. Further, a method for producing this anhydrous acid, namely by dehydration of the hydrated form in the environment of boiling alkanols with 1 to 4 carbon atoms

Description

The present invention relates to the 2-methoxyimino-2- (2-amino-1,3-thiazol-4-yl) acetic acid syn-form of the formula

NH,

C-COOH

II ^N \ och ₃ and method of its production. This novel, hitherto undescribed substance is a preferred starting material for the preparation of 2-methoxyimino-2- (2-amino-1,3-thiazol-4-yl) acetyl chloride syn-formate hydrochloride, which thus becomes an easily accessible basic azlucted synthesis product of the so-called 2-methoxyimino-1,3-thiazol-4-yl. aminothiazole beta-lactam antibiotics.

The syn-form of 2-methoxyimino-2- (2-amino-1,3-thiezol-4-yl) acetic acid ethyl ester is known which is hydrolysed in a known manner by the known 2-methoxyimino-2- / 2-acid syn-form. Amino-1,3-thiazol-4-yl (acetic) British Patent 6,025,933 A) This acid is described as an individual crystallizing in the form of needles having a mp of 140-150 ° C, characterized by NMR and 15-spectra. Known data have been confirmed in the reproduction of alkaline hydrolysis, moreover, age has shown that the obtained needle-crystalline substance is a hydrated form. For example, when reacted with ethanolic hydrochloric acid or a nitric acid solution in methyl ethyl ketone, the hydrochloride aonohydrate or hydronate monohydrate provides similar reaction of said amino acid with phosphorus trichloride to give only different forms of the hydrochloride of said amino acid. The hydrated form is therefore unsuitable for the preparation of anhydrous salts.

It has been found that the known hydrated acid can be easily and in a high yield converted into a new, anhydrous syn-form by the method of the invention, which essentially consists in the syn-form of the hydrated 2-methoxyiaino-2- / 2-emino acid. The 1,3-thiazol-4-yl / acetic acid is dehydrated in a C prostředí-C alk alkanol environment, preferably ethanol, at the boiling temperature of the reaction mixture.

The obtained new syn-form of the acid crystallizes in contrast to the known hydrated form (needles) in the form of well-developed platelets, which melt at 20-220 ° C with decomposition. The structure of this anhydrous acid was confirmed by elemental analysis,

NMR and IR spectra. For further details, see the following exemplary embodiment.

Example

a) 2-Methoxylmino-2- (2-amino-1,3-thlezol-4-yl) acetic acid hydrated form

42.5 g of 2-methozyimino-2- (2-amino-1,3-thiazol-4-yl) acetic acid syn ester form were added to a mixture of 190 ml of ethanol and 230 ml of 1N sodium hydroxide and the reaction mixture was stirred for 3 hours. hours at 50 ° C. It is evaporated to dryness in vacuo, the residue is taken up in 200 ml of water, extracted with 100 ml of ethyl acetate, the aqueous layer is separated and acidified with dilute hydrochloric acid (1: 1) to pH 2.8. The crystalline acid formed is filtered off with suction, washed with 20 ml of acetone and 30 ml of petroleum ether. After air-drying, 38.0 g of the desired hydrated acid is obtained as needles. The thus obtained and isolated product contained 2.1% of water, m.p. 143-150 ° C.

b) 2-Methoxyimino-2- (2-amino-1,3-thiazol-4-yl) acetic acid syn-form

20.0 g of the previous acid, a water content of 12.1% of theory, are added to 100 ml of ethanol and the mixture is heated under reflux for 30 minutes. The reaction mixture is cooled, the precipitated anhydrous acid is filtered off with suction, washed with 30 ml of acetone, 30 ml of petroleum ether and air-dried. 202 DEG-206 DEG C. (decomposition), a water content of 0.1% by weight, is obtained. The spectrum and the spectrum were identical to those of the hydrated form except for the absence of water.

Anelysis for C 8 H 11 N 2 O 6 S:

Calculated: C 35.82: H 3.51} N 20.89} S 15.93}

Found: C, 35.66; H, 3.56; N, 20.57; S, 15.73.

Claims (2)

Attachment of the Invention Synthetic form of anhydrous 2-methoxyimino-2- (2-amino-1,3-thiazol-4-yl) acetic acid of the formula C — COOH II. . . - 2. A process for the preparation of 2-methoxyimino-2- (2-amino-1,3-thiazol-4-yl) acetic acid syn-form according to claim 1, wherein the syn-form of hydrated 2-methoxyimino-2 acid. - (2-Amino-1,3-thiazol-4-yl) acetic acid is dehydrated in a C 1 -C 4 alkanol, preferably ethanol, at the boiling point of the reaction mixture