2,2,2-Trichloroethyl Phosphorodichloridate

[18868-46-7]  · C2H2Cl5O2P  · 2,2,2-Trichloroethyl Phosphorodichloridate  · (MW 266.26)

(preparation of phospholipids via phosphotriester intermediates)

Physical Data: mp 28-30 °C.

Form Supplied in: white solid; commercially available.

Preparative Method: a solution of 2,2,2-Trichloroethanol (1 equiv), Triethylamine (1 equiv) in THF is added to a solution of Phosphorus Oxychloride (1 equiv) at -70 °C.1

Preparation of Phospholipids.

2,2,2-Trichloroethyl phosphorodichloridate (1) is a convenient source of phosphate for the synthesis of oligonucleotides. The reaction of (1) with amines provides phosphoramidochloridates, which are reacted with glycerols to provide phosphotriesters. The amine and trichloroethanol protecting groups can be efficiently and selectively cleaved, providing phospholipids.

An example of this strategy is the reaction of (1) with aniline to provide the phosphoramidochloridate (2).2 Reaction of phosphoramidochloridate (2) with 1,2-distearoylglycerol (3) afforded phosphotriester (4) (eq 1). Both protecting groups were selectively removed in subsequent steps.3

1. Grzeskowiak, K. S 1980, 831.
2. Lammers, J. G.; van Boom, J. H. RTC 1977, 96, 216.
3. For additional examples, see: (a) Lammers, J. G.; van Boom, J. H. RTC 1979, 98, 243. (b) Ogilvie, K. K.; Beaucage, S. L.; Schifman, A. L.; Theriault, N. Y.; Sadana, K. L. CJC 1978, 56, 2770. (c) Trigalo, M.; Charon, D.; Szabo, L. JCS(P1) 1988, 2243.

Roger Harrington

Ciba-Geigy, Summit, NJ, USA

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