Trifluoroacetic acid → HCID 86620330, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-{[2-(diisopropylamino)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate (2.3 g, 4.3 mmol) in dimethylformamide (30 mL) at 0° C. was treated with trifluoroacetic acid (1.6 mL, 21.5 mmol, 5.0 eq.) and stirred at 0° C. for an additional 10 minutes. Peracetic acid (726 μL of a 32%/wt solution in acetic acid, 10.8 mmol, 2.5 eq.) was added over 5 minutes, then the mixture was allowed to warm to room temperature. Stirring was continued until analysis of an aliquot by LC/MS indicated complete conversion of 2-{[2-(diisopropylamino)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate to 2-{[2-(diisopropylamino)ethyl]sulfonyl}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate (typically about 2 hours). The reaction mixture was diluted with ethyl acetate (800 mL) and washed with a 1:1 mixture of 0.2M aqueous Na2S2O4 and saturated aqueous NaHCO3 (2×800 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered, and treated with excess hydrochloric acid (4.0M in dioxane). The resulting hazy solution was concentrated under vacuum to give 2-{[2-(diisopropylamino)ethyl]sulfonyl}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)-phosphorodiamidate hydrochloride as a clear oil (2.53 g, 100% yield). MS (ES+): m/z=564 [C18H39Cl4N3O4PS+H]; 1H NMR (CD3OD): δ=1.44 (t, J=6.3 Hz, 12H), 3.41-3.52 (m, 8H), 3.64-3.87 (m, 16H), 4.53 (q, J=5.5 Hz, 2H); 31P NMR (CD3OD): δ=18.01.

Provenance & Evidence