Methanol → Trifluoroacetic acid

Participants

Reaction Steps

A solution of ethyl 2-amino-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (Preparation 50D, 4 mg, 7.63 μmol) and 10% aqueous sodium hydroxide (0.2 mL) in methanol (0.2 mL) was stirred under nitrogen at 60° C. for 1.5 hr and then room temperature overnight. 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 (2S)-2-amino-2-methyl-4-(3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoic acid, TFA (3 mg, 4.82 μmol, 63.1% yield) as a white solid. The compound had an HPLC retention time=3.07 min (condition C); LC/MS M+1=497.3; 1H NMR (400 MHz, MeOD) δ ppm 8.14 (1H, s), 7.86 (1H, d, J=7.7 Hz), 7.54-7.64 (5H, m), 7.22-7.30 (2H, m), 3.03 (2H, t, J=7.0 Hz), 2.90 (2H, t, J=7.0 Hz), 2.83 (1H, td, J=13.1, 5.0 Hz), 2.65 (1H, td, J=13.0, 5.0 Hz), 2.26 (1H, td, J=13.5, 4.7 Hz), 2.10 (1H, td, J=13.5, 4.7 Hz), 1.62 (3H, s).

Provenance & Evidence