Preparation of 1,5-Dioxaspiro[5.5]undecan-3-one.

Abstract

A. 3-Amino-3-(hydroxymethyl)-1,5-dioxaspiro[5.5]undecane. A 1-L single-necked, round-bottomed flask is equipped with an egg-shaped, Teflon®-coated magnetic stirring bar (3.5 cm x 1.5 cm), capped with a rubber septum, flame-dried under vacuum, and cooled under an argon atmosphere (Note 1). After cooling to ambient temperature (21-23 °C), to the flask is added anhydrous N,N-dimethylformamide (DMF, 365 mL, 0.78 M) via cannula. Subsequently, tris(hydroxymethyl)aminomethane hydrochloride (45.0 g, 286 mmol, 1.00 equiv) (Note 2 and 3) is added in a single portion as white crystalline solid. The reaction vessel is immediately resealed with a rubber septum under inert atmosphere and stirring is commenced (Figure 1). To this white suspension is added 1,1-dimethoxycyclohexane (50.0 mL, 47.4 g, 329 mmol, 1.15 equiv) via syringe in one portion (Note 4). Lastly, to the off-white slurry is added para-toluenesulfonic acid monohydrate (p-TsOH•H2O, 1.63 g, 8.57 mmol, 0.03 equiv) as a solid in one portion quickly, immediately replacing the rubber septum to maintain an inert atmosphere.