Methanol → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 88A, 28 mg, 0.068 mmol), sarcosine hydrochloride (42.8 mg, 0.341 mmol), sodium acetate (28.0 mg, 0.341 mmol), anhydrous sodium sulfate (1 g), anhydrous MeOH (1 mL), and anhydrous 1,2-dichloroethane (3 mL) was stirred at 60° C. under nitrogen for 1 hr. After the mixture was cooled to room temperature, sodium cyanoborohydride (8.58 mg, 0.136 mmol) was added. The reaction mixture was stirred at room temperature for 30 min and then filtered. The filtrate was concentrated. 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-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)acetic acid, TFA (25 mg, 0.041 mmol, 60.7% yield) as a white solid. The compound had an HPLC retention time=3.39 min. (condition C); LC/MS M+1=484.4. 1H NMR (400 MHz, MeOD) δ ppm 8.08 (1H, d, J=7.9 Hz), 7.77 (2H, d, J=7.3 Hz), 7.54-7.72 (5H, m), 4.45 (2H, s), 4.08 (2H, s), 3.07-3.19 (4H, m), 2.94 (3H, s).

Provenance & Evidence