The title compound was prepared by several related methods. The sodium salt generated from tetraisopropyl methylenediphosphonate (I) and NaH was alkylated with 3,5-di-t-butyl-4-hydroxybenzyl chloride (II) in refluxing THF to afford the target arylethyl diphosphonate
Alternatively, tetraisopropyl methylenediphosphonate (I) was alkylated with the benzyl alcohol (III) or with the dimethyl benzylamine (IV) in the presence of strong bases such as NaH or NaO-t-Bu
In a related procedure, the dimethyl benzylamine (IV) was quaternized with iodomethane, and the resultant ammonium salt (V) was then condensed with the sodium salt of diphosphonate (I) (1). Other reported alkylating reagents included the bis-benzyl methyl amine (VII), prepared by Mannich reaction of methylamine with 2,6-di-t-butylphenol (VI) and formaldehyde, and the tris-benzyl amine (VIII), prepared by alkylation of ammonia with the benzyl chloride (II)
In a further method, condensation of benzyl alcohol (III) with methanol in the presence of a catalytic amount of HCl afforded the corresponding methyl ether (IX), which was then reacted with diphosphonate (I) in the presence of NaH to furnish the target arylethyl diphosphonate (1). Optionally, diphosphonate (I) was condensed with the benzyl acetate ester (X), prepared from benzyl chloride (II) and potassium acetate in acetone