Lithium hydroxide, monohydrate → 4-(Hydroxymethyl)oxane-4-carboxylic acid

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Reaction Conditions

Reaction Steps

Lithium hydroxide monohydrate (16.7 g, 398.5 mmol) was added to a solution of 4-(hydroxymethyl)tetrahydropyran-4-carboxylic acid ethyl ester (25.0 g, 132.8 mmol) in 4.5:1 methanol/water (220 mL). The mixture was heated to reflux for 40 minutes and the methanol removed in vacuo by concentration using a bath temperature no higher than 45° C. The aqueous layer was then extracted into diethyl ether (4×100 mL) and the combined ether layers washed twice with 2M sodium hydroxide (15 mL). The combined aqueous base layers were cooled to 0° C., acidified to pH 3.0 with 8M aqueous hydrochloric acid, saturated with solid sodium chloride and extracted with ethyl acetate (8×250 mL). The combined organic layers were dried over magnesium sulfate, concentrated in vacuo. The white fluffy powder residue was recrystallized from the minimum amount of methylene chloride/hexanes to afford pure 4-(hydroxymethyl)tetrahydropyran-4-carboxylic acid (17.05 g, 80%).

Provenance & Evidence