Cesium bicarbonate → 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

関与物質

反応条件

反応手順

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-96a and I-96b were prepared in 1 step from racemic compound I-14 and 5-hydroxypicolinic acid methyl ester according to the following procedure: 3-bromo-5-(4-(trifluoromethoxy)phenyl)-4,5-dihydroisoxazole (1.0 equiv), 5-hydroxypicolinic acid methyl ester (1.2 equiv), and cesium hydrogencarbonate (1.50 equiv) are suspended in N,N-dimethylforamide (0.32 M with respect to dihydroisoxazole. The mixture is then degassed with argon after which it is heated to 130° C. for 4 h after which point there is only desired product and corresponding acid visible by LC/MS. The reaction is allowed to cool to room temperature and quenched by pouring into a solution of ammonium chloride in water (30% by weight, 0.08 M with respect to dihydroisoxazole). The aqueous phase is extracted with ethyl acetate (2×), dried over sodium sulfate, filtered and concentrated to product a brown solid which could be recystallized from absolute ethanol to provide racemic 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-96 that was isolated by filtration as a white solid (25% yield). These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=383.8 m/z. Activity: A

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