Dimethylformamide → 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Participants

Reaction Conditions

Reaction Steps

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-195a and I-195b were prepared according to the following procedure: racemic dihydroisoxazole I-178 (1.0 equiv) was dissolved in N,N-dimethylforamide (0.1 M with respect to isoxazole) after which ammonium chloride (3.1 equiv) and sodium azide (1.5 equiv) were added. The reaction was then heated in an oil bath to 120° C. for 4 h after which point it the reaction was transferred to a separatory funnel with excess ethyl acetate and water. The organic layer was washed with water and saturated sodium chloride, dried over sodium sulfate and concentrated to provide a crude oil that was purified by flash silica gel chromatography (hexanes/ethyl acetate) to provide the desired racemic tetrazole I-195. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=393.2 m/z. Activity: A

Provenance & Evidence