Hydrochloric Acid → Trifluoroacetic acid

Participants

Reaction Steps

To a stirred 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, 34 mg, 0.050 mmol) and water (0.025 mL) in diethyl ether (1.5 mL) was added 6 N aqueous HCl (50 μL, 0.300 mmol). The mixture was stirred at room temperature for 30 min. The ether layer was removed and the residue was mixed with MeOH (0.5 mL) and 2 N aqueous sodium hydroxide (0.5 mL, 1.000 mmol). After being stirred at room temperature for 30 min, the mixture was acidified with TFA to get a clear solution. Purification using reverse phase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration and lyophilization gave 2-amino-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid, TFA (10 mg, 0.015 mmol, 30.6% yield) as a white solid. The compound had an HPLC retention time=3.40 min. (condition C); LC/MS M+1=484.1; 1H NMR (400 MHz, MeOD) δ ppm 7.91 (1H, d, J=7.7 Hz), 7.78 (2H, d, J=8.1 Hz), 7.59-7.72 (3H, m), 7.33 (1H, s), 7.30 (1H, dd, J=8.0, 1.7 Hz), 4.00 (1H, t, J=6.3 Hz), 3.04-3.10 (4H, m), 2.74-2.95 (2H, m), 2.12-2.36 (2H, m).

Provenance & Evidence