Water → Trifluoroacetic acid

Participants

Reaction Steps

A mixture of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 88A, 20 mg, 0.049 mmol), diethanolamine (18.68 mL, 0.195 mmol), 1,2-dichloroethane (1 mL) and sodium triacetoxyborohydride (31.0 mg, 0.146 mmol) was stirred at room temperature under nitrogen for 2 days. Sodium cyanoborohydride (20 mg, 0.318 mmol) was then added. The mixture was stirred at room temperature for 1 hr before water (1 mL) was added. The aqueous layer was extracted with dichloromethane (2×1 mL). The combined organic solutions were concentrated under reduced pressure. 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 2,2′-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylazanediyl)diethanol, TFA (15.6 mg, 0.025 mmol, 51.6% yield) as a white solid. The compound had an HPLC retention time=3.20 min. (condition C); LC/MS M+1=500.1; 1H NMR (400 MHz, MeOD) δ ppm 8.06 (1H, d, J=7.9 Hz), 7.77 (2H, d, J=7.5 Hz), 7.56-7.72 (5H, m), 4.55 (2H, s), 3.94 (4H, t, J=5.2 Hz), 3.39 (4H, t, J=4.8 Hz), 3.07-3.18 (4H, m).

Provenance & Evidence