Phosphoramidic dichloride, bis(2-chloroethyl)- → 2-{[2-(diethylamino)ethyl]thio}ethyl N,N-bis(2-chloroethyl)phosphorodiamidate

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Reaction Conditions

Reaction Steps

To a solution of 2-[2-(diethylamino)ethylthio]ethanol (420 mg, 2.4 mmol) in tetrahydrofuran, cooled to −78° C., was added with stirring lithium bis(trimethylsilyl)amide (1.0M in tert-butyl methyl ether, 2.62 mL, 2.62 mmol), followed by a solution of N,N-bis(2-chloroethyl)phosphoramidic dichloride (680 mg, 2.62 mmol) in tetrahydrofuran (10 mL). The orange reaction mixture was stirred at −78° C. for 90 minutes, then allowed to warm to −20° C. and ammonia gas bubbled through it for 10 minutes. The reaction mixture was stirred for an additional 10 minutes, then poured into a separatory funnel containing water (200 mL) and dichloromethane (200 mL). The organic and aqueous layers were separated, and the aqueous layer washed with dichloromethane (3×200 mL). The organic layer and washings were combined, dried over magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography on a 25 g silica column, eluting with 90% chloroform/10% (5% ammonium hydroxide in methanol), to give 2-{[2-(diethylamino)ethyl]thio}ethyl N,N-bis(2-chloroethyl)phosphorodiamidate as a clear oil, 97% pure by HPLC. MS (ES): m/z=380 [C12H28Cl2N3O2PS+H+].

Provenance & Evidence