Hydrochloric Acid → 4,5-Dihydro-5-methyl-3,4-diphenyl-5-isoxazolol

Participants

Reaction Conditions

Reaction Steps

The deoxybenzoin oxime (Step 1) was dissolved in anhydrous THF (565 mL) under a nitrogen atmosphere. The solution was cooled to −20° C. The solution was treated with lithium diisopropylamide (2 M, 800 mL, 1.60 mol) while allowing the reaction temperature to warm to 10-15° C. The reaction mixture to was cooled to −10° C. to −20° C. and anhydrous ethyl acetate (218 mL) was added to the solution while allowing the reaction temperature to rise to a maximum of 25° C. and held for 30 minutes at 25° C. The reaction mixture was cooled to about 0° C. Water was added to a quench flask and cooled to 0-5° C. The pre-cooled reaction mixture was transferred from the reaction flask to the quench flask while maintaining the temperature of the quench mixture below 25° C. The quenched mixture was cooled to 0-5° C. Hydrochloric acid (12 M) was added to the mixture, keeping the temperature below 25° C. during the addition by controlling the addition rate and stirred until all the solids dissolve (˜5 minutes). The pH of the stirred mixture was measured to be pH 3-4. The layers were separated and the organic layer was removed. Heptane was added to the organic layer with stirring. The organic layer was distilled until the pot temperature reached 90-91° C. The solution was cooled to 5° C. and filtered. The solid was washed with two 300 mL portions of ethyl acetate-heptane (20/80), cooled to 5° C. The solid product was dried on the funnel for several hours then dried at ambient under vacuum with a nitrogen sweep over the weekend to yield the isoxazoline (108.75 g, 57.7%).

Provenance & Evidence