Some medicinal chemistry---preparation of an antibiotic

We want to convince you that this chemistry is useful and also that it works in more complicated molecules so we are going to describe in part the preparation of a new antibiotic, ofloxacin. The sequence starts with an aromatic compound having four fluorine atoms. Three are replaced specifically by different nucleophiles and the last is present in the antibiotic itself. As a reminder of the first 

The next step is the first nucleophilic aromatic substitution. The amino group attacks in the position ortho to the carbonyl group so that an enolate intermediate can be formed. When the charge returns, the first fluoride is expelled. 

Treatment with base (NaH can be used) now converts the OH group into an alkoxide and it does the next aromatic nucleophilic substitution. In this reaction we are attacking the position meta to the ketone so we cannot put the negative charge on the oxygen atom. The remaining three fluorines must stabilize it by the inductive effect we described earlier. 

When this charge returns to restore the benzene ring, the second fluoride is expelled and only two are left. One of these is now displaced by, for the first time, an external nucleophile—an amine. It is easy to predict which one because of the need to stabilize the charge in the intermediate. 

This displaces the third fluorine and all that is left is to hydrolyse the ester to the free acid with aqueous base (Chapter 12). Every single reaction in this quite complicated sequence is one that you have met earlier in the book, and it forms a fitting climax to this section on the addition-elimination mechanism for aromatic nucleophilic substitution. We now need to mention two other less important possibilities. 

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