Chlorotrimethylsilane → 3-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-3,3a,4,5-tetrahydronaphtho[1,2-c]isoxazol-3-ol

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Reaction Conditions

Reaction Steps

To a stirred solution of 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime (I-1, 4.03 g, 21.50 mmol) and diisopropylethylamine (6.83 mL, 39.1 mmol) in anhydrous THF (50 mL) was added TMS-Cl (2.75 mL, 21.50 mmol) dropwise at 0° C. under nitrogen. The mixture was stirred at 0° C. for 30 min. The previously prepared LiTMP solution was added dropwise at −78° C. under nitrogen. After the mixture was stirred at the same temperature for 30 min, a solution of methyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate (I-3, 5.3 g, 19.54 mmol) in anhydrous THF (10 mL) was added dropwise at −78° C. The solution was stirred at −78° C. for 30 min and then warmed to 0° C. over 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution (25 mL) and water (20 mL). The mixture was mixed with EtOAc (50 mL), stirred at room temperature for 30 min and filtered through a pad of celite. The filtrate was separated. The aqueous layer was extracted with EtOAc (2×25 mL). The combined organic solutions were washed with brine (50 mL), dried over sodium sulfate and concentrated to give a liquid. Flash chromatography purification (330 g silica gel column, 15-30% ethyl acetate in hexanes) afforded 3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-3,3a,4,5-tetrahydronaphtho[1,2-c]isoxazol-3-ol (5 g, 11.73 mmol, 60.0% yield) as a yellow solid. The compound had an HPLC retention time=3.74 min (condition C); LC/MS M+1=426.9.

Provenance & Evidence