Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

Reaction of sodium salt of 4-(3-hydroxypropyl)pyridine (I) with diisopropyl p-toluenesulfonyloxymethanephosphonate (II) afforded diisopropyl ester of the corresponding phosphonomethyl derivative (III), together with 4-cyclopropylpyridine (IV). The ester III was converted into free 3-(4-pyridinyl)propoxymethanephosphonic acid (V). The synthesis of 3-(2-amino-4-pyridinyl)propoxymethanephosphonic acid (XVI) started from 4-(3-benzoyloxypropyl)pyridine (VII) via the N-oxide VIII which on heating with phosphoryl chloride afforded the 2-chloro derivative IX. Compound IX was debenzoylated with sodium methoxide to give 2-chloro-4-(3-hydroxypropyl)pyridine (XI). Condensation of sodium salt of XI with tosylate II afforded diisopropyl 3-(2-chloro-4-pyridinyl)propoxymethanephosphonate (XIII) and 2-chloro-4-cyclopropylpyridine (XIV). Deprotection of the ester groups in XIII with bromotrimethylsilane gave 3-(2-chloro-4-pyridinyl)propoxymethanephosphonic acid (XV). The chlorine atom in position 2 was replaced by reaction of compound XV with aqueous ammonia at 200 °C under catalysis with copper(II) sulfate. This gave 3-(2-amino-4-pyridinyl)propoxymethanephosphonic acid (XVI) as the final product.