Methyl iodide → Ethyl 2-(diphenylmethyleneamino)-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate

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Reaction Conditions

Reaction Steps

To a clear solution of ethyl 2-(diphenylmethyleneamino)-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 91A, 560 mg, 0.829 mmol) in anhydrous THF (20 mL) was added 1 M THF solution of lithium bis(trimethylsilyl)amide (4 mL, 4.00 mmol) dropwise at 0° C. under nitrogen. The mixture was stirred at the same temperature for 60 min. before half the amount of the required iodomethane (0.25 mL, 4.00 mmol) was added. The mixture was stirred at 0° C. for 20 min. before the rest of the iodomethane was added. The mixture was stirred at 0° C. for an additional 50 min. and saturated aqueous ammonium chloride solution (5 mL) and water (2 mL) were added. The mixture was extracted with ethyl acetate (10 mL and then 2×5 mL). The combined ethyl acetate extracts were dried (sodium sulfate) and concentrated under reduced pressure. Flash chromatography purification (24 g silica gel column, 5→50% ethyl acetate in hexanes) afforded ethyl 2-(diphenylmethyleneamino)-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (300 mg, 0.435 mmol, 52.5% yield) as a glassy solid. The compound had an LC/MS M+1=690.4.

Provenance & Evidence