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# United States Patent [19J 

# Chauvette et al. 

# [54] PROCESS FOR 3-CHLORO CEPHALOSPORIN NUCLEUS 

[75] Inventors: Pamela A, Chauvette; Robert R. Chauvette, both of Indianapolis, Ind. 

[73] Assignee: Eli Lilly and Company, Indianapolis, Ind. 

[21] Appl. No.: 183,918 

[22] Filed: Sep. 4, 1980 

[51] Int. CJ.3 ............................................ C07D 501/04 

[52] U.S. Cl. ..................................... 544/016; 424/246 

[58] Field of Search ................... 544/16; 260/245.2 R; 424/246 

## [56] References Cited 

<img src='content_image/928190.jpg'>

J. Altman et al., "7.,-N-Amidinocephalosporins", J. Med. Chem., 1975, vol. 18, No. 6, pp. 627-630. 

F. J. Lund, "6/3-Amidinopenicillanic Acids-Synthesis and Antibacterial Properties", Recent Advances in the 

## U.S. PATENT DOCUMENTS 

## OTHER PUBLICATIONS 

Chemistry of /3-Lactam Antibiotics, Ed. J. Elks, Special› ist Publication-Chemical Society, No. 28, 1977, pp. 25-45. 

B. Baltzer et al., "Degradation of Mecillinam in• Aque› ous Solution", J. Pharm. Sci., 68, No. 10, Oct. 1979, pp. 1207-1215. 

Primary Examiner-Nicholas S. Rizzo 

Attorney, Agent, or Firm-William B. Scanlon; Arthur R. Whale 

## [57] ABSTRACT 

7-Amino-3-hydroxy-3-cephem esters react with a chlo› rinating agent, e.g. phosgene, thionyl chloride and pref› erably PCl3-DMF to provide 7/3-[(dimethylaminome› thylene)amino]-3-chloro-3-cephem esters which on re› action with a carboxylic acid, a percarboxylic acid, or a phenol, having a pH in water of about 2-5, afford 7 /3- formamido-3-chloro-3-cephem esters, and correspond› ing 2-cephem esters. Percarboxylic acids provide 7 /3- formamido-3-chloro-3-cephem ester I-oxides. The 7- formamido derivatives provide the 7-amino-3-chloro-3- cephem ester on acid hydrolysis. The 7-amino-3-chloro esters are useful for preparing antibiotics. 

## 12 Claims, No Drawings 

# [11] 4,281,117 

# [45] Jul. 28, 1981 

