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

Temperature

0 °C

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.

1. temperatureto warm to room temperature
2. filtrationthe mixture was filtered
3. concentrationconcentrated under vacuum to a thick syrup
4. additionThis syrup was diluted with isopropyl acetate (200 mL)
5. washwashed with water (3×200 mL)
6. dry with materialThe isopropyl acetate layer was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customto give a clear oil
10. customThis oil was purified on a 30 mm×150 mm silica gel column

ORD record

ord-4dfd22e15ec041fd8f57c0a2a66e2fde

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07655799B2