DE2408171C3 - Silyl oxazolidinone compounds and processes for their preparation - Google Patents

Description

Products. ..

These compounds are particularly valuable and useful in the manufacturing process for 6-acylam-dopenicillanic acid, 7-Acylamidocephalosporic acid and 7-Acvlamido-desacetoxy-cephalosporanoic acid, in turn are of importance due to their usefulness as therapeutic agents in medicine, as additives too Animal feed and as technically important intermediate products.

Are from the group of the silyl reactants The working methods have preferably become common property based on hexamethyldisilazane by Birkofer (Chem. Abstr. 59, 2826-1963) and the Rühlman's working method based on

according to claim 1, characterized in that a 2-oxazo! idiPii) n of the formula

C. -C / ' CH O N
/ /
H O
\ - H \

in which Ri and R2 have the above meaning, with an alkylchlorosilane of the general formula

Cl-Si-R ₁₁

in which R ₃ , R ₄ and R _{5 are} as defined above, reacts in the presence of an organic tertiary base.

The invention relates to a group of compounds of the general formula

R ₁

CH

-CH

N-Si-R ₄

in which Ri and R2 are hydrogen, alkyl groups of low molecular weight or aryl groups and R ₃ , R4 and R5 are alkyl groups of lower molecular weight

weight to move, being from the

2 «the basic compounds that are formed, such as ammonia and dialkylamines, have to be removed because these compounds react strongly with the acylating agents. For this reason, the silyl ester of 6-APA must also be isolated. The fact that these temperatures up to 150 ⁰ C has to be applied, leads to a limitation in the use of solvents for the reaction of the silylation and consequently to a more cumbersome process; this is sometimes based on the use of an excess of the securing agent as a medium in which the conversion takes place, and then afterwards "A posteriori" d: e dissolution is carried out in the desired solvent The trialkylchlorosilanes have the disadvantage similar to the Ν, Ν'-alkylsilyldiphenylureas, which generate precipitates which are deposited on the product from which the preparation of the silyl ester is sought; the surface activity is changed and thereby prolonged Long treatments for 4s are caused, which have a significant influence on the practical feasibility of the method. As for the quality and purity of these solutions, the hydrochloride of the tertiary base, which is formed when chlorosilane acts on 6-APA in the presence of, for example, triethylamine, leads to more or less colored compounds depending on the temperature and reaction The same happens with 7-aminocephalosporanic acid (7-ACA) and to an even greater extent with 7-amino-desacetoxycepha- «losporanic acid (7-ADCA), which in the state of increased" purity is practically insoluble in all common organic solvents in the presence of an excess of organic bases.

These previously known and occurred difficulties and disadvantages are overcome with the aid of the 3-alkylsilyl-2-oxazolidiones according to the invention; With These new compounds can be used to create silyl esters of 6-APA, 7-ACA under mild conditions and 7-ADCA produce in a variety of organic solvents, both protic or can be aprotic, as well as low dielectric constant and all of which are familiar to those skilled in the art.

The new Silylverbindungcn the above general -ormel be prepared by reacting a 2-oxazolidinone with n _10, for example, trimethylchlorosilane in the presence of tertiary organic bases is reacted. The general procedure leads in the specific case to 3-trimethylsilyl-2-oxazolidinone; this connection is shown below with the abbreviation TMSO ^:
while for the trimethylsilyl group the abbreviation . _έ TMS is used.

TMSO is created when 2-oxazolidinone is converted (a) with trimethylchlorosilane (b) or with dimethyldichorsilane in the presence of tertiary bases such as triethylamine, N-ethylpiperidine, quinoline and picolines as typical examples; these bases bind the acid with the formation of the corresponding hydrochlorides; the Implementation proceeds according to the following reaction scheme:

(a) O

CH ₃ (Cl)

N-H + Cl-Si-CH ₃ (b)
CH,

(-HCl)

II CH ₃ (Cl)

(I) O N-Si-CH ₃

il ο

CH,

Have both 3-trimethylsilyl-2-oxazolidinone (TMSO) and 3-chlorodimethylsilyl-2-oxazolidinone (CMSO) see as excellent reactants for the preparation of silyl esters of 6-APA, 7-ACA and 7-ADCA proven; the base-catalyzed formation reaction of these esters proceeds according to the following scheme

I + H ₂ NR-COOH

40 CH ₃ (Cl)

ON —H + H ₂ NR-COOSi-CH ₃ (11)

Il ο

CH ₃

and is carried out in a suitable medium, namely in an organic solvent, which is preferably characterized by a lower solubility for the hydrochloride of the tertiary base and in which the compounds (a) and (b) and the silyl derivative (I) easily dissolve . In the production of the new silylating agents cheap and widely available on the international markets starting materials are used, such as trimethylchlorosilane and dimethylchlorosilane and 2-oxazolidinone, which can be conveniently obtained from monoethanolamine and urea, as well as the tertiary amines, which are easy recovered from the hydrochlorides and reused in the process.

The reaction between the oxazolidinone and a halotrialkylsilane, such as trimethylchlorosilane is carried out under mild conditions at temperatures from room temperature up to 40 ⁰ C, preferably at low temperatures in the case of dimethyldichlorosilane with removal of the halogen with a tertiary base. For example, a solution of 2-oxazolidinone and trimethylchlorosilane in 1,2-diehlorethane is prepared and triethylamine is added using minimum amounts which are predetermined by the stoichiometry of the reaction; the hydrochloride of the tertiary base precipitates practically immediately and is filtered off.

in this bt-R denotes the structural unit penam, cefam or Cefem, with which according to the trivial nomenclature of Böse and Manas (Synthesis of Penicillin Cephalosporin C and Analogues; Marcel D e k k r r, Inc. New York, 1969, p. 2) that in penicillins and cephalosporins present binuclear framework is called.

An important advantage that distinguishes the new agents for silylation over the known agents is based on the fact that a compound is released in the reaction medium, namely 2-oxazolidinone, which, unlike the usual reaction partners, not only does not intervene in the course of the reaction and remains in solution without affecting the equilibrium; which was also found to be they favor the acylation of II to HI and the quality and yield of conversion to IV improve by subsequent treatment with water.

CH, (Cl) / (III) R ₁ -CO-NH-R-COOSi-CH ₃

CH ₃

(H ₂ O)

(R ₂ -CH ₂ OH)

(IV)

R ₁ -CO-NH-R-COOH

The use of these silylating agents is characterized in that a 2-oxazolidinone is present in the reaction medium is released, which is released even when the agent is treated with water; this This fact enables easy characterization of these reactants. The advantage of these intermediates, For example, 2-oxazolidinone when using TMSO is easy to convert to active Intermediate compounds, the 3-acyl-2-oxazolidinones, when used as acylating agents acid anhydrides, acid chlorides or other active functional derivatives of Carboxyl group can be used, in which case the

24 08

-leaktion runs according to the following simplified scheme

(V) O N-H

R ₁ -COX

Il ο

(-HCl)

(VI) O Ν — CO — Rj

Il ο

In this scheme, V denotes the intermediate 2-oxazolidinone and VI denotes the intermediate 3-acyl-2-oxazolidinone and X is an active derivative group of a carboxylic acid. The elimination of the hydrogen chloride at the formation of VI takes place in the presence of tertiary organic bases or if these are not present in the presence of agents with the same effect as triethylamine pivalate, which is usually used in the manufacturing process for penicillins and cephalosporins use finds the presence of these intermediates is described below in a few examples in order to take advantage of the particular advantages of the in The new silylating agent in question is released 2-oxazolidinone, through which the process for Production of the antibiotics mentioned is improved to show.

The useful activity of the new silylating agent, for example TMSO is reflected in the ability of that of a tertiary base silyl ester, for example, formed min of 7-ADCA in methylene chloride within 30 in the presence of catalytic amounts, when heated under reflux at about 40 ⁰ C , while with the known agent hexamethyldisilazane 24 to 48 hours are required for the reaction. If TMSO is reacted with 6-APA in methylene chloride, the ester is formed in 5 minutes at the same temperature.

Under the previous conditions, the new silylating agents also do not cause epimerization of the Penicillins and cephalosporins; this is extremely important because of those described in the literature Epimers of these antibiotics have no biological activity and are therefore cause for a low level Yield of biologically active product. The known disadvantage arises from the use of N, N-bis (trimethylsilyl) acetamide, like this by G u t ο w s k i (Tetraht dron Letters, 1779; 1970) and Vanderhaegheetal. (Tetrahedron Letters, 285, 1972). Epimerization and secondary decomposition reactions also occur when using tertiary organic bases when the silylating agent is trimethylchlorosilane or Hexamethyldisilazan or Trimethylsilyldiäthylamin and the reaction by means of the temperature is activated.

The advantages that TMSO possesses and its special features

»(III) + O Ν — Η

C.
O

The results obtained with this silylating agent appear surprising.

example 1
3-trimethylsilyl-2-oxazolidinone (TMSO)

Triethylamine (60 ml; 0.42 mol) was added to a solution of 2-oxazolidinone (30.5 g; 0.35 mol) in methyl ethyl ketone (50 ml) and the mixture was cooled in an ice-water bath with stirring. Trimethylchlorosilane (60 ml; 0.44 mol) was then gradually added over 15 minutes and the temperature was maintained at 35 to 40 ° C. during the addition. Stirring was then continued for 45 minutes without cooling and care was taken that the temperature did not decrease; the reaction mixture was filtered to separate off the triethylamine hydrochloride, which was then washed with a large amount of methyl ethyl ketone. The filtrate and washing liquid were combined and the solvent was ^{stripped off under reduced pressure and heating in a water bath (40 °} C.); A more or less light brown oil was obtained, which was mixed with n-heptane (50 ml) and then filtered in order to separate off residual triethylamine hydrochloride. The yield of the crude product was practically quantitative.

The dissolved n-heptane (approx. 25%) was initially distilled off from the lower organic phase separated by settling; then the vacuum was amplified and recovered a colorless liquid, which corresponded TMSO, yield 52.2 g, or 93.7%, · d == 1.040 (20 ⁰ C); Bp = 97 ° C / 3.5 mm Hg (d = density).

Alcoholysis with methanol in methylene chloride and evaporation of the solvent gave 1.593 g TMSO obtained 0.871 g of 2-oxazolidinone. 2-oxazolidinone calculated 54.67%, found 54.6%.

Example 2
S-triethylsilyl ^ -oxazolidinone (TESO)

The procedure was as in Example 1 and trimethylchlorosilane with triethylchlorosilane (63.3 g, 0.62 mol) replaced, otherwise the same conditions were observed. The title compound was found as a colorless liquid in obtained the same yield. 2-oxazolidinone calculated

4232%, found 42.70%; distilled at 100 ^° C. / 2-4 mm.

Example 3
S-trimethylsilyl-S-methyl ^ -oxazolidinone

The procedure was as in Example 1 with 5-methyl-2-oxazolidinone (35.43 g; 035 mol) instead of 2-oxazolidinone. With otherwise the same procedure, the crude product was obtained in a practically quantitative yield The title compound was a light brown liquid by methanolysis in methylene chloride 5-methyl-2-oxazolidinone obtained; found 58.25%, calculated 5837%.

15 Example 4

5-phenyl-3-triethylsilyl-2-oxazolidinone

According to Example 1, 5-phenyl-2-oxazolidinone (57.11 g; 035 mol) with triethylchlorosilane (633 g; 0.42 Mol) reacted. After evaporation of the solvent, the crude compound became practically quantitative Yield obtained. Methanolysis gave 5-phenyl-2-oxazolidinone; found 69.05%, calculated 6933%.

Example 5
A) 3-Trimethylsilyl-2-oxazolidinone (TMSO) I.

A solution of 2-oxazolidinone (52.20 g; 0.6 mol) in 1,2-dichloroethane (650 ml), which was cooled with stirring in an ice-water bath, was first treated with trimethylchlorosilane (107.0 ml; 0 , 8 mol) and then with another solution of triethylamine (105.0 ml; 0.75 mol) in 1,2-dichloroethane (100 ml). The reaction was moderately exothermic and the temperature was kept at 25-30 ⁰ C; the reaction mixture was stirred well for 60 min and protected from room moisture. The precipitated triethylamine hydrochloride was then filtered off and the solvent was removed from the filtrate by heating to 40 ^° C. under reduced pressure. The residue was treated with ethyl acetate and then filtered, whereby residues of triethylamine hydrochloride were separated. Finally the solvent was removed; 9830 g of golden yellow liquid were obtained in a practically quantitative yield.

Distillation under reduced pressure gave 95 g of 3-trimethylsilyl-2-oxazolidinone as a colorless liquid with d - 1.03 (18 ° C.) and boiling point - 97 ° C./3.5 mm Hg. The compound was insoluble in water and n-heptane, soluble in the majority of common solvents.

Triethylamine hydrochloride (93.9 g) was in practical quantitative yield isolated; by treatment with sodium hydroxide (caustic soda) the recovered organic base and reused for another reaction.

B) Trimethylsilyl ester of 6-APA (II)

i-APA (4230 g; 0.2 mol) was suspended in methylene chloride (500 ml) with vigorous stirring and treated with TMSO (41.2 ml; 0.26 mol), quinoline (23.5 ml, 0 , 2 mol) and triethylamine (10 ml) were added, the temperature being kept at 35.degree. After 15 minutes, a practically colorless liquid was obtained. Stirring was continued until the temperature reached 20 ^° C.

C) Trimethylsilyl ester of the compound IV ₁ (III)

A mixture of D (-) - «- azidophenyl acetic acid (0.2 Mol) activated with CSDF (0.2 mol) in methylene chloride according to the method described in the literature (A. L Palomo; Afinidad No. 284, 151, 1971) gradually to -15 ° C over the course of 30 minutes solution 5-B which had been cooled and quinoline (23.5 ml) added in advance was added. It was then for 120 min stirred at 0 ° C and obtained a solution of III.

D) 6- (D (-) - λ-AcidophenylacetamidoJ-penicillanic acid, IV

The solution obtained above, clouded by the hydrochloride of the tertiary base, was added with stirring 150 ml of water are added, the pH is adjusted to 2.1-2.4 with hydrochloric acid and the organic phase is passed through Settling separated. This was then washed with water and over anhydrous sodium sulfate dried; a solution of the title compound was obtained. A solution was then found Sodium 2-ethylhexanoate in methyl isobutyl ketone (90 ml - 47%) was added and the mixture was diluted with n-heptane; it fell immediately the sodium salt of IV, which isolated by filtration gave the pure product (75 g, 98%); confirmed by IR spectrum, optical activity and bio test (990 μg / mg).

Example 6
A) 3-Trimethylsilyl-2-oxazolidinone, (TMSO) I

A solution of 2-oxazolidinone (104, 40 g; 1.2 mol) and triethylamine (210 ml; 1.5 mol) in 1,2-dimethoxyethane (80 ml) was cooled with stirring in an ice-water bath and made up with another solution Trimethylchlorosilane (214.0 ml; 1.6 mol) in 1,2-dimethoxyethane (200 ml) added. This was followed by vigorous stirring for 60 minutes with exclusion of moisture. The hydrochloride formed of the base was then filtered off (185.0 g) and the The solvent is removed under reduced pressure; 196.5 g of I were obtained, which distilled in vacuo and resulted in a practically colorless liquid.

B) Trimethylsilyl ester of 7-ADCA, II

7-ADCA (42.80 g; 0.2 mol) was suspended in methylene chloride (500 ml) and treated with quinoline (46.0 ml; 0.4 mol), TMSO (41.2 ml; 0.26 mol) and Triethylamine (10 ml) added; the addition took place with exclusion of moisture and at a temperature of 35 ^° C .; A solution was obtained after 30 minutes with thorough stirring. Depending on the purity and crystalline state of the 7-ADCA, by keeping the reaction at room temperature, a solution was obtained within 60-120 minutes.

QTrimethylsilyl ester of 7 (D (-) - a-Azido-phenylacetamido) -desacetoxycephalosporanic acid, 111

A mixture of D (-) - «- azidophenylacetic acid, activated as in Example 5-C, was gradually im The course of 30 min is added to solution 6-B at 0 °.

The mixture was then stirred for 120 min at room temperature and a solution of III was obtained.

₍₎ D) 7 (D (- ) - «■ Azidophenylacetamido) -

desacetoxycephalosporanic acid, IV

The above solution was treated in the same way as in Example 5-D; obtained 75 g of sodium

salt (98%), its identity by IR spectrum (0-lactam core and azido function) as well as by Biotest) has been confirmed.

Example 7

A) S-Trimethylsilyl ^ -oxazolidinone, (TMSO) I

A solution of 2-oxazolidinone in accordance with the amounts given in Example 5-A was initially added Triethylamine and then trimethylchlorosilane, diluted in 1,2-dichloroethane, are added. The reaction mixture was Worked up as in Example 5 and 95.2 g of I isolated by distillation under reduced pressure.

B) Trimethylsilyl ester of 7-ADCA, II

A suspension of 7-ADCA (21.4 g; 0.1 mol) in methylene chloride (150 ml), treated with triethylamine (5 ml) and TMSO (25 ml), was stirred at room temperature with exclusion of moisture, whereby a Solution of II obtained When using a larger amount of triethylamine, the time for preparation the solution shortened.

C) Derivative of the trimethylsilyl ester

of 7 (D (-) - «- Amino-phenylacetamido) -desacetoxycephalosporanic acid, 111

The obipe solution was gradually added at 0 ⁰ C for another solution of a mixed anhydride, which in methylene chloride with the sodium salt of N (1-methyl-2-ethoxy-vinyl) - D (-) -a-aminophenylacetic acid (37.24 g ; 0.12 mol) and ethyl chloroformate (11.57 g; 0.12 mol); the mixture was then stirred for a further 90 minutes and a solution of III was obtained.

D) 7 (D (-) - «- Amino-phenylacetamido) -desacetoxycephalosporanic acid

150 ml of water and hydrochloric acid were added to the above solution until the pH had adjusted to 1.5-2. The aqueous phase was poured off, brought to pH 4.2 with sodium hydroxide solution and the precipitated product was filtered off, washed with acetone and dried; were obtained 30.4 g (83%) of title compound, confirmed by IR spectrum, iodometric determination (990μg / mg) and optical activity [x]><* - +143.7 ⁰ C (C = l, 0% HC10.5n).

Example 8
A) 3-Trimethylsilyl-2-oxazolidinone, (TMSO) I

Oxazclidinone (52.20 g; 0.6 mol) was dissolved in 1,2-dimethoxyethane (300 ml) and then diluted with allyl acetate (500 ml); then trimethylchlorosilane (107.0 ml; 0.8 mol) and then N-ethylpiperidine (79.2 g; 0.7 mol) were added with thorough stirring, the temperature being kept ^{at 30 ° C. by means of cooling.} After 60 min the precipitated hydrochloride of the base was filtered off and ethyl acetate was distilled off from the fiI under reduced pressure; 395 g of solution of I. were obtained. Distillation of the solvent gave 97.65 g of silyl reactants (TMSO).

B) Trimethylsilyl ester of 6-APA II

In the solution of I and 1,2-dimethoxyethane (200 g a 24%) 6-APA (42.80 g; 0.2 mol) was suspended with thorough stirring and treated with triethylamine (10 ml) offset. After 60 minutes of reaction at room temperature, a solution of II was obtained.

C) trimethylsilyl ester

of 6- (3,0-chlorophenyl-5-methyl-

4-isoxazolylcarboxamido) penicillanic acid, IH

In addition to the above solution, another solution of 3 (2-o-chlorophenyl) -5-methyl-4-isoxazolylcarboxylic acid (0.2 mol) was gradually activated as described in the literature (AL Palomo and E. Torrens; Afinidad No. 290 , P. 993, 1971) and triethylamine as an HCl acceptor; the pH was kept at 5 to 6 and, after stirring for 60 minutes at 0 ^° C., a solution of IH was obtained which was clouded by the precipitated hydrochloride.

D) 6 (3-o-chlorophenyl-5-methyl-4-isoxazolylcarboxamido) peniculanic acid, IV

Methyl isobutyl ketone (250 ml) was added to the above preparation, and the precipitate formed was filtered off and treated with water (10 ml); after stirring for 15 minutes, a 45% solution was obtained Sodium 2-ethylhexanoate in n-butanol was added and the mixture was left to rest for 120 minutes. The The sodium salt was filtered off and washed with n-heptane; 93.9 g of the title compound were obtained in a yield of 98.7%, confirmed by the IR spectrum and iodometric evaluation (953 μg / mg).

Example 9

A) 3-chlorodimethylsilyl-2-oxazolidinone, (CMSO) I

Another solution of dichlorodimethylsilane was added to a solution of 2-oxazolidinone (104.40 g; 1.2 mol) in 1,2-dimethoxyethane (500 ml) diluted with ethyl acetate (500 ml) and cooled in an ice bath with stirring (156.7 ml; 1.3 mol) in ethyl acetate (500 ml) and then tributylamine (222.4 g; 1.2 moles) was added while the temperature was maintained at 0 ⁰ C. After stirring for 30 minutes, the tributylamine hydrochloride formed was filtered off and the more volatile solvent was stripped off under reduced pressure. The resulting liquid was diluted with n-heptane (2000 ml) and, after allowing it to stand for 15 minutes, the lower phase was separated off; 215.0 g of I were obtained in the form of a yellowish liquid; the yield was practically quantitative. Distillation under reduced pressure gave a practically colorless liquid.

B) chlorodimethylsilyl ester of 6-APA, II

In the same way as in Example 5-B, CMSO was used with the silylating agent prepared as above. obtained a solution from II from TMSO.

C) chlorodimethylsilyl ester of 6- (2,6-dimethoxybenzamido) penicillanic acid, III

2,6-Dimethoxybenzeo acid was activated in the same way as in Example 5-C and as there with a 6n solution of the ester, prepared according to Example 9-1 offset; a colorless solution of IH was obtained.

D) 6- (2,6-dimethoxybenzamido) penicillanic acid, IV

ds It was made in the same manner as in Example 5-1 worked and the sodium salt of the title compound i obtained in an analogous yield; the connection was identified by their IR spectrum and iodometrically.

45

Example 10

A) 3-Trimethylsilyl-2-oxazolidinone, (TMSO) I

By working according to Example 5-A and triethylamine was replaced by the equivalent amount of quinoline, the compound I was obtained.

B) Trimethylsilyl ester of 6-APA, II

The reaction partner just prepared was used in the same way as in Example 5-B to form a solution made from II

C) Derivative of the trimethylsilyl ester
of 6- (D (-) - <x-amino-p-hydroxyphenylacetamido) -

penicillanic acid, HI

The solution just obtained was added to another mixed anhydride solution made from D (-) - <x-amino-p-hydroxyphenylacetic acid, ethyl acetylacetate and pivaloyl chloride according to a method described in the literature (E. Dane and T. D ο c k η e r Ber, 98,789,1965) had been obtained; it the procedure was as in Example 7-C and a solution of the compound III was obtained.

D) 6- (D (-) - a-amino-p-hydroxyphenylacetamido) -penicillanic acid, IV

In the manner described in Example 7-D, the title compound was isolated and identified by its IR spectrum as well as iodometric determination and biotest (975 μ ^ / η ^) identified and confirmed.

Example 11
A) S-Trimethylsilyl ^ -oxazolidinone, (TMSO), I.

It was in the same way as in Example 8-Λ proceed with the equivalent amount of tripropylatin instead of N-ethylpiperidine and then as in Example 1 continued to work; Compound I was obtained in an identical yield.

B) Trimethylsilyl ester of 7-ADCA, II

The procedure was as in Example 6-B using the previous silylating agent and a Obtain solution from II.

C) trimethylsilyl ester

of 7- (-hexamine-hexamethylenetetramine-

phenylacetamido) -desacetoxy-

cephalosporanic acid, IH

(X-hexamethylenetetramine (urotropine) phenylacetic acid was prepared by adding α-chlorophenylacetic acid by their silyl ester, made from the acid and TMSO in the presence of triethylamine, replaced and then treated with urotropine and finally released the ester using isopropanol would.

Hexamethylenetetraminophenylacetic acid (31.07 g; 0.1 mol) was added to methyl chloride (300 ml), ^{the mixture was cooled to 0 °} C. with stirring, and dimethylformimino-N-chloride chlorosulphite (0.1 mol) was gradually added; after 120 min the whole thing was slowly _{poured onto a solution of H 1} prepared from 21.4 g of 7-ADCA, at a temperature of ⁰ ° C. and in the same way as in example 6-C; a solution of III was obtained.

171

D) 7- (α-Hexamethylenetetramine-phenylacetamido) -desacetoxycephalosporanic acid

Isopropanol (100 ml) was added to the above filtered acid and the ^{mixture was stirred at 0 °} C. for 30 minutes. The precipitate was filtered off, washed with n-heptane and dried at low temperature; The title compound was obtained (45 g; 90%), which was identified and confirmed by its IR spectrum and by iodometric measurement.

It was worked in the same way as in Example 5-D 'jnd hydrochloric acid up to a pH of 1.5-2 added, the aqueous solution poured off and adjusted to pH 4.2; 7 - (<x-Aiminophenylacetamidoj-desacetoxycephalosporanic acid off (29.2 g; 82%).

Example 12 E) 3-Benzoyl-2-oxazolidinone, VI

To a solution of 2-oxazolidinone (4.68 g; 0.05 mol) in 1,2-dichloroethane (60 ml) were benzoyl chloride (5.6 ml; 0.05 mol) and triethylamine (7.0 ml; 0.05 mol) added and stirred at room temperature for 30 minutes.

It was then concentrated under reduced pressure and ethyl acetate was added; it was then filtered in order to separate off the hydrochloride formed from the base. The filtrate was partially evaporated, the residue was diluted with n-heptane and the precipitated solid substance was collected on the filter. After washing with water and drying, 3-benzoyl-2-oxazolidinone (5.94 g; 90%) was obtained. From absolute ethanol pearlescent panels crystallized, mp. 166- 170 ⁰ C. A portion of this material in ethanol with a katalytisehen amount of sodium ethylate was added at room temperature gave ethyl benzoate and immediately reacted with aniline benzanilide.

C) Trimethylsilyl ester of 6- (benzamido) -penicillanic acid, III

A solution of the trimethylsilyl ester of 6-APA according to Example 5-B was prepared ('/ β of the solution) and 3-benzoyl-2-oxazolidinone (3.3 g; 0.025 molj added, at room temperature for 30 min was stirred; a solution of III was obtained.

D) 6- (Benzamido) penicillanic acid, IV

The above solution was mixed with water, stirred and adjusted to pH 2 with hydrochloric acid. the

so organic layer was separated over anhydrous dried em sodium sulfate and then treated with sodium 2 ethyl hexanoate and treated with n-heptane (250 ml diluted; the sodium salt of IV precipitated out, which by means of its IR spectrum and iodometric evaluation

ss (988 µg / mg) was identified; Yield 8.07 g or 95%.

Example 13 E) 3- (p-Methoxybenzoyl) -2-oxazolidinone, Vl

A solution of 2-oxazolidinone (4.35 g; 0.05 mol) ii 1,2-dimethoxyethane (35 ml) was treated with p-Methoxyben zoylchlorid (8.53 g; 0.05M) was added at 0 ⁰ C and gekühl / I-picoline (4 ml) and N-ethylpiperidine (5.66 g) were added. The mixture was then stirred for 60 min at the same temperature and then diluted with n-hepta (250 ml); the precipitate was filtered off, washed with water and dried and erga

10.50 g (95%) solid substance, which after recrystallization melted from ethanol at 152-4 ° C.

Qtrimethylsilyl ester of 7- (p-methoxybenzamido) -desacetoxycephalosporanic acid, 111

The compound according to Example 13-E (0.025 mol) was added to a solution of the trimethylsilyl ester of 7-ADCA in methylene chloride (containing 0.025 mol) and the mixture was ^{stirred for 60 minutes at a temperature of 30 °} C .; a solution of St.

D) 7- (p-Methoxybenzamido) -desacetoxycephalosporanic acid, IV

The above solution, 13-C, was treated further in the same way as in Example 7-D and the sodium salt the title compound obtained by its IR spectrum has been confirmed.

Example 14
E) 3- (p-chlorobenzoyl) -2-oxazolidinone, VI

In the same way as in Example 13-E, methylene chloride was used instead of 1,2-dimethoxyethane, with p-Chlorobenzoyl chloride (8.75 g; 0.05 mol) in place of p-methoxybenzoyl chloride and with quinoline instead of jS-picoline obtained the compound 14-E (10.5 g; 93.6%), after recrystallization from ethanol at 162-65 ° C melted.

C) trimethylsilyl ester
of 7- (p-chlorobenzamido) -cephalosporanic acid, III

To a solution of the trimethylsilyl ester of 7-ACA in methylene chloride (containing 0.025 mol) was the Compound 14-E (0.025 mol) was added and the whole was stirred for 60 min at a temperature of 20 ° C .; receive a solution from III.

D) 7- (p-chlorobenzamido) -cephalosporanic acid, IV

The above solution, 14-C, was made in the same manner as in Treated Example 5-D and obtained the sodium salt of the title compound, which is indicated by its IR spectrum was identified.

Example 15
E) 3- (p-nitrobenzoyl) -2-oxazolidinone, VI

In the same manner as in Example 13-E, p-nitrobenzoyl chloride (9.27 g; 0.05 mol) was used in place of p-Methoxybenzoyl chloride obtained the compound 15-E (10.71 g; 90.3%), which after recrystallization from ethanol melted at 233 -5 ° C.

C) trimethylsilyl ester
of 6- (p-nitro-benzamido) -penicillanic acid, III

To a solution of the trimethylsilyl ester of 6-APA

(0.025 mol) in methylene chloride, the compound 15-E (0.025 mol) was added and the whole 120 min at Stirred at room temperature; a solution of III was obtained.

D) 6- (p-nitroben2, amido) -penicillanic acid, IV

The above solution, 15-C, was treated in the same way as in Example 5-D and the sodium salt of Title compound obtained, which is identified by its IR spectrum and by iodometric measurement would.

Claims (1)

Patent claims: 1. Silyloxazolidinone compounds of the formula R ₂ CH CH N-Si-R ₄ \ in which Ri and R ₂ each represent a hydrogen atom, an aryl group or a Ci-C ₃ alkyl group or one of them represents a chlorine atom. The invention relates in particular to 3-trimethylsilyl-2-oxazolidinone and other similar compounds, to processes for the production of d.eser compounds as well as to processes for the production of penicillins or cephalosporins with the help of d.eser