N,N,N',N'-Tetrakis(2-chloroethyl)phosphorodiamidic Chloride → Di[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]sulfide

Temperatur

2.5 °C

5-Hydroxy-3-thiapentyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate, 174 mg (0.387 mmol), and N,N,N′N′-tetrakis(2-chloroethyl)phosphorodiamidoyl chloride, 363 mg (0.996 mmol), were dissolved in 15 mL anhydrous tetrahydrofuran and cooled to 0-5° C. in an ice-water bath. Potassium tert-butoxide, 0.4 mL of 1 M solution in tetrahydrofuran (0.4 mmol), was added over a 10-15 minute period, and the reaction mixture kept at 0-5° C. for another 30 minutes under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 43 hours. Additional potassium tert-butoxide and N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidoyl chloride were added over the next 4 days to drive the reaction to completion. After 4.5 days, the reaction mixture was diluted with ethyl acetate; and the ethyl acetate layer separated, washed with water and brine, then dried over anhydrous magnesium sulfate, and the ethyl acetate removed under vacuum. The crude di[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]sulfide, 630 mg, was twice purified by preparative HPLC, and the product fractions combined and lyophilized, giving di[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]sulfide, compound 1CC, as a colorless oil, compound 1CC, 56 mg (18% yield), identified by HPLC and 1H and 31P NMR. Mass spectrum: 779 (C20H40Cl8N4O4P2S+4+H+).

1. temperatureto warm to room temperature
2. customthe reaction to completion
3. waitAfter 4.5 days
4. customand the ethyl acetate layer separated
5. washwashed with water and brine
6. dry with materialdried over anhydrous magnesium sulfate
7. customthe ethyl acetate removed under vacuum
8. customThe crude di[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]sulfide, 630 mg, was twice purified by preparative HPLC

ORD-Eintrag

ord-a9b8f3fc2e6c4993b410040a2f8c955a

Quelldatensatz

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07262182B2