6-APA synthesis

6-APA chemical synthesis could be shortly resumed as a controlled hydrolysis of a penicillin. At first indeed, we protect the carboxylate group as a siloxane (two molecules of penicillin at the time). This is a simple nucleophilic substitution on dichloro dimethyl silane, where two atoms of chlorine are displaced (HCl produced is neutralized by Et3N). The carboxylate groups are now unable to react with electrophiles, and the attention can be focused on 6-nitrogen.

The chlorinating agent PClworks on the enol form of the molecule, and as a result we get a chloro-imine.The chloro imine is highly reactive and adding n-butanol we get (through an addition-elimination reaction), an imine-ether. In the last step we get the hydrolysis at the same time of the carboxyl groups and the imine-ether (we will get an esther and a silane as elimination products) and we extract in acqueous solvent (the amino group in position -6 is protonated).