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

Temperature

-25 °C

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%).

1. customequipped with a nitrogen gas inlet, mechanical stirrer
2. temperaturemaintaining an internal temperature no higher than -15° C
3. customthe cooling bath was removed
4. temperatureto warm to room temperature over 1 hour
5. additionsaturated aqueous sodium sulfate (325 mL) added over 15 minutes
6. temperatureThe mixture was cooled to -15° C.
7. additionethyl acetate (250 mL) was added
8. filtrationthe flocculent white precipitate filtered over a pad of celite
9. washThe celite pad was washed with ethyl acetate (7×450 mL)
10. washthe filtrate washed with brine (200 mL)
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated in vacuo
13. dissolutionThe residue was dissolved in the minimum amount of ethyl acetate
14. filtrationfiltered through a sintered glass funnel
15. additioncontaining silica gel (40 g)
16. washeluting with ethyl acetate
17. concentrationthe filtrate concentrated in vacuo

ORD record

ord-a2a60e711585488084946f3e68c90da9

Source dataset

uspto-grants-1999_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05932595