2-Mercaptoethanol → 5-Hydroxy-3-thiapentyl N,N,N',N'-tetrakis(2-chloroethyl)phosphorodiamidate

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Reaction Conditions

Reaction Steps

2-mercaptoethanol (400 μL, 5.7 mmol) was dissolved in methanol (8 mL), and NaOH in methanol, (3.56 mL of 4M, 14.25 mmol) was added. The solution was cooled to 0° C. and 2-(4-bromobenzenesulfonyloxy)ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate (8.35 mL of 0.82M solution in toluene, 6.84 mmol) was added, and the reaction mixture allowed to warm to room temperature. After 12 hours, the mixture was filtered, neutralized to pH 7 with 1M aqueous H3PO4, and concentrated under vacuum to a thick syrup. This syrup was diluted with isopropyl acetate (200 mL), and washed with water (3×200 mL). The isopropyl acetate layer was dried over MgSO4, filtered, and concentrated under vacuum to give a clear oil. This oil was purified on a 30 mm×150 mm silica gel column using a gradient of 70:30 ethyl acetate/hexanes to 100% ethyl acetate to give 2-{[2-(hydroxy)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate as a clear oil (1.41 g, 55% yield). 1H NMR (CDCl3): δ 1.64 (bs, 1H), 2.76 (t, 2H, J=5.9 Hz), 2.84 (t, 2H, J=6.3 Hz), 3.40-3.47 (m, 8H), 3.62-3.69 (m, 8H), 3.76 (t, 2H, J=5.9 Hz), 4.18-4.23 (m, 2H); 31P NMR (CDCl3): δ 17.58.

Provenance & Evidence