ChemInform Abstract: The Synthesis of 1-Amino-2-hydroxy- and 2-Amino-1-hydroxy-substituted Ethylene-1,1-bisphosphonic Acids and Their N-Methylated Derivatives

A synthesis of 2-amino-1-hydroxyethylene-1,1-bisphosphonic acid 3 has been developed from N -phthaloylglycine via dimethyl 2-( N -phthaloylamino)acetylphosphonate 1 . The preparation of the N -methylated and N , N -dimethylated derivatives 4 and 5 has been achieved by the reaction of 3 with formic acid and formaldehyde. The synthesis of 1-amino-2-hydroxyethylene-1,1-bisphosphonic acid 9 (RR′H) and its N -methylated and N , N -dimethylated analogues has been achieved by the reaction of phosphorus trichloride and phosphorous acid with the appropriate O -benzyl protected hydroxyacetamide, followed by catalytic hydrogenolysis of the protecting group.