Acetic Acid → Tert-butyl 1-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Participants

Reaction Steps

A solution of 3-(4-(bromomethyl)phenyl)-5-(3-(pyridin-2-yl)-4-(trifluoromethyl)-isoxazol-5-yl)-1,2,4-oxadiazole (2.52 g, 5.59 mmol) and tert-butyl azetidine-3-carboxylate, acetic acid (1.82 g, 8.39 mmol) in N,N-dimethylformamide (40 mL) cooled with an ice-water bath was added triethylamine (2.34 mL, 16.8 mmol) drop-wise. The reaction mixture was stirred for 30 minutes, diluted with ethyl acetate (350 mL), washed with a 10% aqueous solution of lithium chloride (2×100 mL), washed with water (100 mL), washed with brine (100 mL), and dried over anhydrous sodium sulfate. Concentration gave a crude product which was triturated with methanol. The resulting solid was collected by vacuum filtration. The filtrate was concentration and purified by silica gel chromatography (eluting with Hexanes/ethyl acetate-4/1) to yield additional product. The material was combined to give tert-butyl 1-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (2.46 g, 83% yield).

Provenance & Evidence