Deprotection of phosphate moieties

The 2-cyanoethyl group, which protects the phosphate moiety, generates acrylonitrile as a by-product when deprotected with concentrated ammonia water. Acrylonitrile may cause 2-cyanoethylation through addition reaction to the nucleobase moiety. As a method to avoid the side reaction of acrylonitrile, a weak base reagent such as diethylamine/acetonitrile solution, instead of generally used concentrated ammonia water, can be used to deprotect the 2-cyanoethyl group while maintaining binding with the solid support, followed by cleavage from the solid support and deprotection of the protecting group of the nucleobase moiety.

Reaction data

Deprotection of 2-cyanoethyl group by ammonia water and reaction of thymidine with byproduct acrylonitrile

Deprotection of 2-cyanoethyl group by diethylamine

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