(R)-3-Pyrrolidinol → (3R)-1-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)pyrrolidin-3-ol

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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), 3R-Pyrrolidinol (21.23 mg, 0.244 mmol), sodium triacetoxyborohydride (31.0 mg, 0.146 mmol) and dichloromethane (1 mL) was stirred at room temperature overnight. The mixture was concentrated and dissolved in methanol. HPLC purification (Column: Waters XBridge C18, 19×250 mm, 5-nm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 25-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min) and concentration gave the titled compound (18.8 mg, 0.039 mmol, 80% yield) as a solid. The compound had an HPLC retention time=2.15 min. (Column: Supelco Ascentis Express C-18, 4.6×50 mm, 2.7 um; Solvent A=0.05% TFA in H2O:MeCN (95:5); Solvent B=0.05% TFA in H2O:MeCN (5:95)); LC/MS M+1=482.1; 1H NMR (400 MHz, MeOD) δ ppm 7.95 (1H, d, J=7.7 Hz), 7.73 (2H, d, J=7.3 Hz), 7.53-7.66 (3H, m), 7.36-7.43 (2H, m), 4.39-4.47 (1H, m), 3.87-4.01 (2H, m), 2.97-3.14 (6H, m), 2.83 (2H, d, J=19.6 Hz), 2.14-2.27 (1H, m), 1.81-1.93 (1H, m, J=13.6 Hz).

Provenance & Evidence