Ethanol → Ethyl 4-(hydroxymethyl)oxane-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 1.5M diisobutylaluminum hydride (DIBAL-H) (419 mL, 629 mmol) in toluene was added to a 3-L Morton flask equipped with a nitrogen gas inlet, mechanical stirrer, low temperature thermometer, 500 mL pressure equalizing funnel, and containing tetrahydropyran-4,4-dicarboxylic acid diethyl ester (70.78 g, 307.4 mmol) in toluene (600 mL) at -40° C., at a rate to maintain an internal temperature no higher than -25° C. The mixture was stirred an additional 10 minutes and anhydrous ethanol (595 mL) was added dropwise over 20 minutes maintaining an internal temperature no higher than -15° C. Solid sodium borohydride (11.6 g, 307.4 mmol) was added in three portions over a 15 minute period, the cooling bath was removed, the mixture allowed to warm to room temperature over 1 hour, and saturated aqueous sodium sulfate (325 mL) added over 15 minutes. The mixture was cooled to -15° C., ethyl acetate (250 mL) was added, and the flocculent white precipitate filtered over a pad of celite. The celite pad was washed with ethyl acetate (7×450 mL), the filtrate washed with brine (200 mL), dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in the minimum amount of ethyl acetate, filtered through a sintered glass funnel containing silica gel (40 g), eluting with ethyl acetate, and the filtrate concentrated in vacuo to afford the hydroxyester, 4-(hydroxymethyl)tetrahydropyran-4-carboxylic acid ethyl ester, as a pale yellow oil (48.5 g, 84%).

Provenance & Evidence