4-Toluenesulfonyl chloride → [2-(2-{2-[2-(2-{4-[2-(2-{2-[2-(2-Azido-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-phenoxy}-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxy]acetic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

To a solution of Compound 26 (254 mg, 0.451 mmol) in pyridine (1.5 ml), 4-dimethylaminopyridine (11 mg, 0.09 mmol) was added; after cooling with ice, p-toluenesulfonyl chloride (130 mg, 0.677 mmol) was added, and this was followed by stirring for 2 hours while heating to 30° C.-40° C. Ice was added thereto to stop the reaction, after which ethyl acetate and water were added. Extraction from ethyl acetate was conducted, and the combined organic phases were washed with a saturated aqueous solution of potassium hydrogen sulfate, a saturated aqueous solution of sodium hydrogen carbonate and saturated brine, and dried with sodium sulfate. Filtration and concentration under reduced pressure were conducted to yield a crude product. The crude product obtained was dissolved in DMF (1 ml), and sodium azide (264 mg, 4.1 mmol) was added thereto. The solution was heated to about 60° C., and this was followed by stirring for 90 minutes. The solution was allowed to cool to room temperature, after which it was diluted with ethyl acetate. After a saturated aqueous solution of sodium hydrogen carbonate was further added, extraction from ethyl acetate was conducted. The combined organic phases were washed with saturated brine, thereafter dried with sodium sulfate. Filtration and concentration under reduced pressure were conducted, after which the concentrate was purified by silica gel column chromatography (Yamazen YFLC Gel, eluent; ethyl acetate solution containing 10% methanol) to yield Compound 27 (colorless oil 196 mg, 73%, 2 steps).

Provenance & Evidence