Dieckman-like condensation

The Bayer synthesis of ciprofloxacin (1) patented in 1981 utilized 2,4-dichloro-5-fluorobenzoyl chloride (15) as the starting material. With the aide of magnesium ethoxide, condensation of acid chloride 15 and diethyl malonate assembled ketone 16, which was subsequently decarboxylated using tosylic acid to form ethyl 2,4-dichloro-5-fluorobenzoylacetate (17) in 82% yield in two steps from 15. A Dieckman-like condensation of 17 with ethyl orthoformate was carried out in refluxing acetic anhydride... 

Dieckman condensation reactions of diesters have been carried out in solid state in presence of a base (like Na or NaOEt) using high-dilution conditions in order to avoid intermolecular reaction. It has been found that the Dieckman condensation of diethyl adipate and pimelate proceed very well in absence of the solvent the reaction products were obtained by direct distillation of the reaction mixture. In this method the diester and powdered Bu OK were mixed using a pestle and mortar for 10 min. The solidified reaction mixture was neutralised with P-TSOH.H2O and distilled to give cyclic compounds (Scheme 14). 

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