Diisopropylamine → 3-Hydroxy-5-[4-(2-tetrahydropyranyl)oxybutyl]isoxazole

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Reaction Conditions

Reaction Steps

13.95 ml of a 15% by weight solution of butyllithium in hexane were added dropwise, at -25° to -15° C., to a solution of 3.08 ml of diisopropylamine in 100 ml of tetrahydrofuran. The mixture was stirred at -20° C. for 15 minutes, after which a solution of 0.990 g of 3-hydroxy-5-methylisoxazole in 10 ml of tetrahydrofuran was added to the mixture at -20° to -10° C. over a period of 10 minutes. The mixture was then stirred at -10° C. for 30 minutes, after which it was cooled to -50° C., and then 3.35 g of 1-bromo-3-(2-tetrahydropyranyl)oxypropane were added to it all at once. The mixture was then stirred at 15°-20° C. for 2 hours, after which it was mixed with 1.20 ml of acetic acid. It was then poured into water. The organic layer was separated and the aqueous layer was adjusted to a pH value of 3 by adding 10% w/v aqueous hydrochloric acid followed by extraction twice with diethyl ether. The combined organic layer and extracts were washed with water, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure, to give a residue, which was subjected to column chromatography through 60 g of silica gel. 1.720 g of the title compound was obtained, as a colorless oil, from the fractions eluted with mixtures of ethyl acetate and hexane ranging from 1:2 to 1:1 by volume.

Provenance & Evidence