Cardioactive iso:sorbide 2-nitrate selective prodn. - by reaction of isomannide with tri:fluoromethane:sulphonic acid halide or anhydride and reaction of the prod. with an (in)organic nitrate

摘要

In a new process for the selective prodn. of isosorbide 2-nitrate (I), (A) isomannide is reacted in an organic solvent with an equiv. amt. of a trifluoromethane sulphonyl halide in the presence of an acid binding agent or with the equiv. amt. of trifluoromethanesulphonic acid anhydride, and (B) the resulting isomannide 2-trifluoromethanesulphonate (II) is reacted in the presence of a solvent and opt. with heating either with an alkali(ne earth) nitrate (opt. in the presence of a crown ether or a phase transfer catalyst) or with an organic nitrate. (I) is useful in the treatment of coronary heart diseases, e.g. angina pectoris. It is a metabolite of isosorbide dinitrate, being formed during "first pass" metabolism of this cpd. in the liver. Use of (I) rather than isosorbide dinitrate is likely to minimise inter-patient differences in response attributable to variations in the degree of first pass metabolism. The process gives (I) uncontaminated by prods. nitrated other than in the 2-position.