Preparation of 3-bromomethyl cephems

Abstract

Preparation of 3-bromomethyl cephem derivatives that are one of the important intermediates in β-lactam antibiotics has been studied. First, 3-methyl cephems were photoreacted with N-bromosuccinimide using 300W tungsten lamp as a light source at 5-10℃ in an atmosphere of nitrogen to give the 3-bromomethyl cephems in 30-45 % yield. Second, 3-bromomethyl-3-cephem derivatives were prepared by reacting 3-exomethylene cephams with 2,6-lutidine-bromine complex. 2,6-Lutidine-bromine complex was prepared by adding a stoichiometric amount of bromine to a solution of 2,6-lutidine in carbon tetrachloride. Using 1,2-dimethoxyethane as a solvent, 3-exomethylene cephams were reacted with 2.5 equivalents of 2,6-lutidine-bromine complex at room temperature to give the 3-bromomethyl cephems in 30-55% yield.