Saturday, 19 May 2012

Laboratory Synthesis Of Ciprofloxacin

 Ciprofloxacin Synthesis
Use: antibacterial
LD50: 122 mg/kg (M, i.v.); 5 g/kg (M, p.o.);
 207 mg/kg (R, i.v.); >2 g/kg (R, p.o.)

 The condensation of 2,4-dichloro-5-fluorobenzoyl chloride (I) with diethyl malonate by means of magnesium ethoxide in ether gives diethyl 2,4-dichloro-5-fluorobenzoylmalonate (II), which is partially hydrolyzed and decarboxylated with p-toluenesulfonic acid water yielding ethyl 2,4-dichloro-5-fluorobenzoylacetate . Condensation of this with triethyl orthoformate  in refluxing acetic anhydride affords ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate (III), which is treated with cyclopropylamine (IV) in ethanol to give ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-cyclopropylaminoacrylate . The cyclization of ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-cyclopropylaminoacrylate with NaH in refluxing dioxane yields 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (V), which is finally condensed with piperazine  in hot DMSO to afford the target compound ciprofloxacin.

Synthesis references
  1. Reddy, P.G.; Baskaran, S.; Microwave assisted amination of quinolone carboxylic acids: An expeditious synthesis of fluoroquinolone antibacterials. Tetrahedron Lett 2001, 42, 38, 6775
  2. Drugs Fut1984,9,(3):179
  3. EP 0078362
  4.  JP 4253963
  5. JP 58074667
  6. US 4620007
  7. US 4670444
  8. EP 657448 
<script type="text/javascript">
ch_client = "sanalpcp";
ch_width = 500;
ch_height = 250;
ch_type = "mpu";
ch_sid = "Chitika Default";
ch_color_site_link = "0000CC";
ch_color_title = "0000CC";
ch_color_border = "FFFFFF";
ch_color_text = "000000";
ch_color_bg = "FFFFFF";
<script src="" type="text/javascript">

No comments:

Post a Comment