1,4-Dioxaspiro[4.5]decan-8-one → 8-Hydroxy-8-(5-thiazolyl)-1,4-dioxaspiro[4.5]decane

Participants

Reaction Conditions

Reaction Steps

A solution of 2-trimethylsilanyl-thiazole (Fluka, 5.0 g, 31.8 mmol) in THF (20 mL) at −78° C. was treated with n-BuLi (2.5 M in hexanes, 15.3 mL, 38.2 mmol) dropped slowly over 10 min. The reaction was stirred for an additional 20 min. at −78° C. A solution of 1,4-dioxa-spiro[4.5]decan-8-one (Aldrich, 6.0 g, 38 mmol) in THF (15 mL) was slowly dropped into the reaction. After addition, the reaction was stirred for an additional 2 hours at −78° C. The reaction was then quenched with water and warmed to room temperature. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a yellow solid. To this solid in THF (20 mL) was added TBAF (1.0 N in THF, 30 mL) at room temperature. The reaction was stirred for 1 hour. The solvent was removed and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, concentrated and then purified by silica gel column on a CombiFlash® system using hexanes and ethyl acetate (from 10% ethyl acetate to 100% ethyl acetate) to afford the title compound as a white solid.

Provenance & Evidence