N-(4-Bromobutyl)phthalimide → ethyl N-[(4-phthalimidobutyl)oxy]acetimidate

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Reaction Steps

Briefly, N-(4-bromobutyl)phthalimide was treated with the anion of ethyl N-hydroxyacetimidate in tetrahydrofuran to yield ethyl N-[(4-phthalimidobutyl)oxy]acetimidate. The product was then treated with hydrazine to release the desired amine, ethyl N-[(4-aminobutyl)oxy]acetamidate, from the phthalimide. The desired amine was isolated from the crude product by removal of phthalazine-1,4-dione by filtration, and was coupled to biotin using dicyclohexyl carbodiimide and N-hydroxy succinimide in dimethylformamide. Acidic hydrolysis of the coupled product, ethyl N-[(4-biotinamidobutyl)oxy]acetamidate, gave the final product, N-(4-aminooxybutyl)biotinamide, V. Other analogous aminooxy linkers may be prepared by variations of the above synthetic procedure. The synthesis of biotin aminooxy linker V is described in more detail and summarized in the reaction scheme presented in Example 1.

Provenance & Evidence