Sodium Hydroxide → alpha-[[2-[[Bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]thio]-4-carboxytoluene

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Reaction Steps

4-(Thiomethyl)benzoic acid was prepared from methyl 4-(bromomethyl)benzoate using the procedure of Org. Syn. Coll. Vol. 3, page 363 (reaction with thiourea in ethanol, followed by hydrolysis of the ester with aqueous sodium hydroxide). 4-(Thiomethyl)benzoic acid, 2 g, was alkylated with 2-(4-bromobenzenesulfonyloxy)ethyl tetrakis(2-chloroethyl)phosphorodiamidate, 15.8 mL of 0.83 M, in 10 mL methanol and 6.25 mL of 4 M sodium hydroxide in methanol. The resulting product after filtration and concentration was a pale yellow oil, which was dissolved in saturated aqueous sodium bicarbonate and washed twice with 100 mL isopropyl acetate. The aqueous extracts were combined, acidified to pH ˜1 with sulfuric acid, and back extracted twice with into 100 mL isopropyl acetate. The isopropyl acetate layers were combined, dried over MgSO4, filtered, and concentrated under vacuum to give α-[[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]thio]-4-carboxytoluene as a pale yellow oil, 5.4 g, with product identity verified by LC-MS.

Provenance & Evidence