反应详情

To a solution of 2-(diethylamino)ethanethiol hydrochloride (840 g, 5 mmol) in methanol (20 mL) was added NaOH (3.8 mL of 4M solution in methanol, 15 mmol, 3 eq.) and 2-(4-bromobenzenesulfonyloxy)ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate (7.0 mL of 0.7M solution in toluene, 4.9 mmol, 0.98 eq.). The mixture was stirred at room temperature until all the 2-(4-bromobenzenesulfonyloxy)ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate was consumed, as determined by HPLC-ELSD. The mixture was acidified to pH 7 with 1.0 M aqueous H3PO4 and concentrated under vacuum to a thick slurry. The slurry was taken up in ethyl acetate (400 mL) and washed with 5% aqueous NaHCO3 (2×400 mL) and then with aqueous HCl (2×400 mL). The acidic aqueous layers were combined and brought to pH>9 with solid NaHCO3, then extracted with ethyl acetate (2×800 mL). The ethyl acetate solution was separated, dried over anhydrous MgSO4, filtered, and concentrated under vacuum to give 2-{[2-(diethylamino)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate as a clear oil (1.05 g, 42% yield). The 2-{[2-(diethylamino)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate was oxidized to 2-{[2-(diethylamino)ethyl]sulfonyl}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate and isolated as the hydrochloride salt using the procedure of Synthetic Example 1. MS (ES+): m/z=536 [C16H35Cl4N3O4PS+H]; 1H NMR (CD3OD): δ=1.36 (t, J=7.4 Hz, 6H), 3.28-3.34 (m, 2H), 3.40-3.50 (m, 10H), 3.65-3.77 (m, 14H), 4.51 (dd, J=5.1, 6.3 Hz, 2H); 31P NMR (CD3OD): δ=18.02.

1. customwas consumed
2. concentrationconcentrated under vacuum to a thick slurry
3. washwashed with 5% aqueous NaHCO3 (2×400 mL)
4. extractionextracted with ethyl acetate (2×800 mL)
5. customThe ethyl acetate solution was separated
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated under vacuum