Lithium Hydroxide → (4-Hydroxyoxan-4-yl)acetic acid

Participants

Reaction Steps

To a solution of ethyl acetate (2.3 mL, 24 mmol) in THF (60 mL), 1M solution of lithium hexamethyldisilazide in THF (24 mL, 24 mmol) is added at −78° C. After stirring 1 hour at the same temperature, tetrahydro-4H-pyran-4-one (1.9 mL, 20 mmol) is added dropwise, and the reaction mixture is allowed to warm to rt over 2 hours. The reaction mixture is diluted with H2O and extracted with EtOAc. The combined organic phases are washed with H2O and dried over Na2SO4. Concentration under reduced pressure and filtration through silica gel give a crude product. To a solution of (4-hydroxy-tetrahydro-pyran-4-yl)-acetic acid ethyl ester (1.85 g) in 1,4-dioxane (5 mL) and H2O (5 mL), lithium hydroxide (235 mg, 9.8 mmol) is added at 0° C. After stirring for 7 hours at rt, the reaction mixture is diluted with H2O and extracted with Et2O. The aqueous layer is acidified with 1N HCl aq. and extracted with Et2O. The combined organic phases are washed with H2O and dried over Na2SO4. Concentration under reduced pressure and filtration through silica gel give a crude product. The material is used in next step without purification.

Provenance & Evidence