Propargyl bromide → 3-(5,5-Dimethyl-3-prop-2-ynyl-3-trifluoromethyl-1,3,4,5-tetrahydrobenzo[c]oxepin-1-yloxy)propan-1-ol

Participants

Reaction Conditions

Reaction Steps

A flask was charged with aluminum (4.1 g of aluminum foil cut into 50 mg pieces, 152 mmol) and mercuric chloride (0.27 g, 1 mmol). The flask was sealed with a septum, flushed with argon, and anhydrous THF (300 mL) was added. Propargyl bromide (80% in toluene, 16.9 mL, 152 mmol) was added via syringe slowly and the resulting mixture was stirred for 30 minutes at 23° C. then warmed to 55° C.-60° C. and stirred an additional 2 hours. A second flask was charged with a 1:2 inseparable mixture of the 4-(2-[1,3]dioxan-2-ylphenyl)-1,1,1-trifluoro-4-methylpentan-2-one and 2-phenyl [1,3]dioxane (15.5 g). Anhydrous THF (150 mL) was added and the solution was cooled to −78° C. The solution of the propargyl aluminum solution was transferred to the ketone solution via cannula. The resulting solution was allowed to warm to 23° C. over a period of 75 minutes then stirred overnight. The reaction was quenched by carefully pouring into an aqueous saturated solution of ammonium chloride (500 mL). The mixture was diluted with diethyl ether (500 mL) and the layers were separated. The aqueous layer was washed with diethyl ether (250 mL) and the organics were combined, dried over sodium sulfate, filtered, and concentrated in vacuo to yield 3-(5,5-dimethyl-3-prop-2-ynyl-3-trifluoromethyl-1,3,4,5-tetrahydrobenzo[c]oxepin-1-yloxy)propan-1-ol as an orange oil (15.0 g) that was used without purification.

Provenance & Evidence