Trifluoroacetic acid → Trifluoroacetic acid

Participants

Reaction Steps

To a solution of the tert-butyl 1-(4-(5-(4-isopropyl-5-(pyridin-2-yl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate in dichloromethane (0.5 mL) was added trifluoroacetic acid (0.5 mL), and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated and purified by preparative HPLC [Prep HPLC: Column: PHENOMENEX® S10 30×100 mm; Gradient time: 10 min; Flow rate=40 ml/min; Solvent A=10% MeOH—90% Water—0.1% TFA; Solvent B=90% MeOH—10% water—0.1% TFA; Start % B=20; Final % B=100.] to yield 1-(4-(5-(4-isopropyl-5-(pyridin-2-yl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate, trifluoroacetic acid salt (2.03 mg, 3.47 mmol, 7.8%). The compound had an HPLC retention time=7.58 min.—Column: Xbridge Ph 3.5 u 4.6×150 mm; Gradient time: 12 min, hold for 3 minutes; Flow rate=2 ml/min; Solvent A=5% MeCN—95% Water—0.05% TFA; Solvent B=95% MeCN—5% water—0.05% TFA; Start % B=10; Final % B=100. LC-MS: M+1=446.3. 1H NMR (500 MHz, MeOD) δ ppm 1.44 (s, 3H), 1.46 (s, 3H), 3.68-3.76 (m, 1H), 4.19 (quin, J=7.15 Hz, 1H), 4.37-4.42 (m, 4H), 4.54 (s, 2H), 7.53 (ddd, J=7.49, 4.74, 1.24 Hz, 1H), 7.70 (d, J=8.25 Hz, 2H), 7.96-8.00 (m, 1H), 8.00-8.05 (m, 1H), 8.30 (d, J=8.25 Hz, 2H), and 8.79 (d, J=4.67 Hz, 1H).

Provenance & Evidence