Various operating conditions have been applied on tetrakis[p‐(halogenomethyl)]‐ and tetrakis[p‐(aminomethyl)]calix[4]arene derivatives to improve the synthesis of the 5,11,17,23‐tetrakis[(diethylphosphono)methyl]‐25,26,27,28‐tetrahydroxycalix[4]arene. Two new, high yield, synthetic pathways have been selected, involving, for the first one, the 25,26,27,28‐tetrahydroxy‐5,11,17,23‐tetrakis[(trimethylamino)methyl]calix[4]arene, tetraiodide, DMF, and 10 equiv. of triethyl phosphite ((EtO)3P), and, for the other one, the 5,11,17,23‐tetra(bromomethyl)‐25,26,27,28‐tetrahydroxycalix[4]arene, CH2Cl2, and only 4 equiv. of (EtO)2P.