Water → HCID 178457310, compound

Participants

Reaction Conditions

Reaction Steps

For the preparation of 69, phosphorus trichloride (21, 875 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added to anhydrous THF. 3-Hydroxypropionitrile (683 μL, 10 mmol) was added dropwise in 10 min to the solution and the mixture was stirred for 25 min at 0° C. to yield 2-cyanoethylphosphorodichloridite (23). Then 25 (1 eq, 10 mmol) that was prepared at the same time in a separate reaction vessel, was added dropwise in 10 min period to the solution containing 23. The mixture was stirred for 15 min at 0° C. to yield 2-cyanoethyl phosphorochloridite-O-2-cyanoethyl diisopropylphosphoramidite (67). Water (180 μL, 10 mmol) and diisopropylethylamine (1,747 μL, 10 mmol) were added dropwise in 10 min period to the solution containing 67. The mixture was stirred for 10 min at 0° C. to yield 2-cyanoethyl hydroxyphosphite-O-2-cyanoethyl diisopropylphosphoramidite (68). Then 29 (1 eq, 10 mmol) that was prepared at the same time in a separate reaction vessel, was added dropwise in 10 min period to the solution containing 68. The mixture was stirred for 35 min at 0° C. to yield bifunctional triphosphitylating reagents 69. The reaction mixture containing triphosphitylating reagent 69 was immediately used in coupling reactions with polymer-bound p-acetoxybenzyl alcohol 78. Further stability studies on 69 using mass spectrometry methods showed that the compound remained stable after 2 months storage at −20° C.

Provenance & Evidence