Carbon Dioxide → 3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To stirred solution of diisopropylamine (1.103 mL, 7.74 mmol) in anhydrous THF (8 mL) was added n-butyllithium (3.10 mL, 7.74 mmol) (2.5 M in hexanes) dropwise at 0° C. under nitrogen. The pale yellow solution was stirred at the same temperature for 20 min before a solution of 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime (intermediate 1, 0.659 g, 3.52 mmol) in anhydrous THF (4 mL) was added dropwise at 0° C. under nitrogen. The mixture was stirred at 0° C. for 1 hour and then transferred to a dry-ice bath. A solution of ethyl 1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (1 g, 3.52 mmol) in anhydrous THF (3 mL) was added dropwise over 4 min. The solution was stirred with dry-ice cooling for 40 min and at 0° C. for 45 min. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (5 mL) and water (3 mL) extracted with ethyl acetate (2×20 mL), washed with brine (10 mL), dried over sodium sulfate, and concentrated to yield a yellow foamy solid. The solid was mixed with anhydrous toluene (20 mL), thionyl chloride (0.514 mL, 7.04 mmol), and pyridine (0.057 mL, 0.704 mmol) was added at room temperature under nitrogen. The reaction mixture was stirred at room temperature for 5 min and at 100° C. for 25 min., concentrated and quenched with saturated aqueous sodium bicarbonate solution (20 mL) and water (10 mL). The reaction mixture was extracted with dichloromethane (20 mL, then 2×10 mL), dried over sodium sulfate, concentrated and chromatographed (40 g silica gel column, 20→100% dichloromethane in n-heptane and then 20%→50% ethyl acetate in n-heptane) to yield 3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (560 mg, 1.375 mmol, 39.1% yield) as a green solid. The compound had an HPLC retention time=3.98 min (condition C); LC/MS M+1=407.8.

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