Ethylene Glycol → 2-Ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one

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Reaction Steps

The crude 2-ethyl ketone (18.7 g) from step (a) was dissolved in 350 ml of toluene under a nitrogen atmosphere. Ethylene glycol (35 ml) and p-toluenesulfonic acid (0.75 g) were added and the reaction was heated at reflux. A Dean & Stark apparatus was used to remove the water. After 3 hrs. the reaction was cooled with an ice-bath and the toluene layer was washed with cold water. The aqueous layer was back extracted with chloroform and the combined organic layers were dried and evaporated to give the crude ketal as an oil (21.5 g). The ketal (21.5 g, 0.072 mol) was dissolved in THF (220 ml) and added dropwise to Vitride (0.216 mol ) in THF (284 ml) . The reaction was stirred overnight, cooled and then water was added to decompose the complex and excess Vitride. The THF layer was separated, dried and concentrated to give the crude 8-methyl-ketal (20.8 g). A portion of the ketal (18.8 g, 0.078 mol) was heated with 125 ml of 1.25N.HCL at 50° C. for 3 hrs. The cooled solution was neutralized with saturated Na2CO3 solution. The aqueous mixture was extracted twice with chloroform, the chloroform layer was dried and concentrated to give the title ketone as an oil (11.6 g).

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