Hydrochloric Acid → Ethyl 2-amino-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 Steps

To a stirred solution of ethyl 2-(diphenylmethyleneamino)-2-methyl-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 93A, 36 mg, 0.052 mmol) in diethyl ether (3 mL) was added 4 M aqueous solution of HCl (120 μL, 0.480 mmol). The mixture was stirred at room temperature for 30 min. The ether layer was separated and extracted with water (1 mL). The aqueous extract was combined with the aqueous layer in the reaction. The mixture was basified with solid potassium carbonate and extracted with ethyl acetate (4×1.5 ml). The combined ethyl acetate extracts were dried (sodium sulfate) and concentrated under reduced pressure to give a glassy solid. The individual enantiomers were separated using a Lux-Cellulose-2 column under SFC conditions (20% IPA with 0.1% EA in CO2). Isomer 1 (Preparation 94A, 8 mg), retention time on chiral HPLC, 8.3 min; Isomer 2 (Preparation 94A, 6 mg), retention time on chiral HPLC, 9.3 min. The absolute stereochemistry at the carbon anchoring the secondary alcohol, of Isomer 1 and Isomer 2, was not determined.

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