The alkylation of sodium saccharin with alkyl halides to produce the intermediates ω-(1,1,3-trioxo-1,3-dihydrobenzo[d]isothiazol-2-yl)-alkanecarboxylic acids can be markedly improved by using microwave irradiation, both in terms of product yield and reaction time. While the process produces high yields with halo esters and halonitriles, the reaction with haloacids, which proceeds smoothly by conventional reflux, gives poorer yields with microwaves. This is due to an acid-base equilibrium produced by the rapid heating of the mixture under irradiation. Esters and nitriles can be converted into the acids by acid hydrolysis, without appreciable loss of the 1,1,3-trioxo-1,3-dihydrobenzo[d]isothiazole ring.
The synthesis of two contaminants of Loratadine, generated when the product is formulated as a syrup, is described. The products, identified as 2-and 4-hydroxymethyl derivatives of the starting compounds, are obtained by the corresponding substitution of the pyridine moiety of Loratadine.
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