United  States  Patent  [19J  Chauvette  et al.  [11]  4,281,117  [45]  Jul.  28, 1981  [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  U.S.  PATENT  DOCUMENTS  OTHER  PUBLICATIONS  4,064,343  4,115,643  4,223,133  4,226,986  12/1977  9/1978  9/1980  10/1980  Chauvette  ..............................  544/16  Kukolja  et al.  ........................  544/16  Bunnell  ..................................  544/16  Matfield  et  al.  .......................  544/ 16  Primary  Examiner-Nicholas  S.  Rizzo  Attorney,  Agent,  or  Firm-William  B.  Scanlon;  Arthur  R.  Whale  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.  [57]  ABSTRACT  12 Claims,  No  Drawings  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  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. 