Dimethylformamide → ethyl 2-(diphenylmethyleneamino)-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

To a stirred clear solution of ethyl 2-(diphenylmethyleneamino)-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 50B, 150 mg, 0.222 mmol) in anhydrous THF (5 mL) was added a 1 M THF solution of lithium bis(trimethylsilyl)amide (333 μL, 0.333 mmol) dropwise at 0° C. under nitrogen. The reaction mixture was stirred at the same temperature for 30 min before iodomethane (50 μL, 0.800 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min and at room temperature for 1 hr. The reaction was not complete. Anhydrous DMF (2 mL) was added, followed by lithium bis(trimethylsilyl)amide (2 mL, 2 mmol) at 0° C. The reaction mixture was stirred at the same temperature for 30 min before iodomethane (0.2 mL) was added. The mixture was stirred at 0° C. for 1 hr and quenched using saturated aqueous ammonium chloride solution (5 mL), ethyl acetate (10 mL), and water (10 mL). The aqueous solution was separated and re-extracted with ethyl acetate (2×5 mL). The combined ethyl acetate extracts were dried over sodium sulfate and concentrated under reduced pressure. Flash chromatography purification using ISCO (4 g silica gel column, 10→100% ethyl acetate in hexanes) afforded ethyl 2-(diphenylmethyleneamino)-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (120 mg, 0.174 mmol, 78% yield) as a solid. LC/MS M+1=689.5.

Provenance & Evidence