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forming groups commonly used to block or protect the C4 carboxylic acid group of the cephalosporins. Exam› ples of such groups include benzyl and substituted ben› zyl such as p-methoxybenzyl, p-nitrobenzyl, and 2,4,6- trimethylbenzyl; diarylmethyl groups such as diphenyl- methyl, 4-methoxydiphenylmethyl, and 4,4’ -dimethox› ydiphenylmethyl; and alkyl and substituted alkyl groups such as t-butyl, t-amyl, 2-iodoethyl, 2-bromoethyl, and 2,2,2-trichloroethyl. Such ester forming groups are functional groups in that they serve for the temporary protection of the carboxy group. After such use they are removed by known hydrolytic or reduction meth› ods to provide the free carboxylic acid. 

The 3-hydroxy-3-cephem ester employed as the start› ing material in the process is prepared as described in U.S. Pat. No. 3,917,587, issued Nov. 4, 1975. 

As mentioned above, when a carboxylic acid or a phenol is used in the process the N-formyl 3-chloro product of the process is obtained as a mixture of the isomeric 2-cephem and 3-cephem and, under basic re- covery conditions, as the 2-cephem isomer. The mixture of isomers or the 2-cephem isomer can be converted to the desired N-formyl 3-chloro-3-cephem ester by the known isomerization method which involves forming the sulfoxide of the 3-chloro ester followed by reduc- tion back to the sulfide form. The formation of the sulfoxide causes the 2,3-double bond to isomerize to the 3,4-position (3-cephem). The isomerization is illustrated by the following reaction scheme. 

The formation of the sulfoxide can be carried out with a peracid such as peracetic, perbenzoic or prefera› bly m-chloroperbenzoic acid in a suitable solvent such as acetone or methylene chloride. The 3-chloro-3- cephem ester sulfoxide is readily isolated by evapora- 65 tion of the reaction mixture and dissolution of the reac› tion product mixture in an organic solvent such as ethyl acetate. The m-chlorobenzoic acid side product is 

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washed from the solution with base and, after the solu› tion of the product is dried and evaporated, the product can be further purified if desired by chromatography. 

The reduction of the N-formyl 3-chloro-3-cephem ester can be carried out by known sulfoxide reduction methods. For example, the reduction methods de› scribed by Murphy et al., U.S. Pat. No. 3,641,014, and by Hatfield, U.S. Pat. No. 4,044,002. The latter method is an especially useful reduction method in that the recovery of the desired product is readily achieved. 

The 7,8-formamido-3-chloro-3-cephem-4-carboxylic acid ester is converted to the desired 7-amino-3-chloro- 3-cephem ester by acid hydrolysis of the N-formyl group. The hydrolysis is carried out in a solvent such as methyl alcohol, tetrahydrofuran, or mixtures thereof • with hydrochloric acid. For example, the N-formyl-3- chloro ester is dissolved in a mixture of methyl alcohol and tetrahydrofuran and the solution is treated at room temperature with a small amount of concentrated hy› drochloric acid. The 7-amino-3-chloro nucleus ester is obtained as the hydrochloride salt. 

In a further aspect of the invention there are provided the intermediates useful in the above process and repre› sented by the following formula 

wherein R’ is hydrogen or a carboxy-protecting group; n is 0 or 1, and salts thereof formed with a strong acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, or a sulfonic acid represented by the formula 

wherein A is phenyl, tolyl, chlorophenyl, or naphthyl. 

The compound of the above formula wherein R’ is hydrogen is obtained by the de-esterification of a car› boxy-protected ester derivative to either the salt form or free base form of the compound. The free acid com› pound can be used as the intermediate in the process which is preferably re-esterified with another ester moi› ety for conversion to the N-formyl product. 

The carboxy-protecting ester groups, R’, are the same carboxy-protecting groups defined for R above and include preferably p-nitrobenzyl, p-methoxybenzyl or diphenylmethyl. 

The salts of the above formula formed with strong acids are stable salts useful for storage of quantities of the compound for subsequent use in the preparation of the 3cchloro nucleus by the process of this invention. As noted above the salts formed with strong acids are sta› ble to chemical degradation of the: 7-amidino side chain. Accordingly, these salts are converted to the free base form prior to use in the second step of the process. 

The strong acid salts are prepared by treating a solu› tion of the free base form of the compound of the above formula in an organic solvent with the strong acid or a 

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