反应详情

(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (4.889 g, 12.72 mmol) was dissolved in hydrogen bromide (33% in AcOH, 30 mL, 428.24 mmol) and stirred at room temperature for 18 h. The compound was purified by preparative HPLC (2 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 05-40% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. The product containing fractions were freeze dried and again treated with hydrogen bromide as described above. The compound was purified by preparative HPLC (3 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 05-40% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. 5-((2R,4S)-2-(4-(Trifluoromethyl)benzyl)piperidin-4-yl)isoxazol-3(2H)-one (3.34 g, 80%) was isolated as a colorless solid. 1H NMR (400 MHz, dmso) δ 1.04-1.15 (m, 1H), 1.35 (qd, 1H), 1.72-1.80 (m, 2H), 2.49-2.58 (m, 1H), 2.61-2.81 (m, 4H), 2.94-3.02 (m, 1H), 5.66 (s, 1H), 7.42 (d, 2H), 7.62 (d, 2H). HRMS Calcd for [C16H17F3N2O2+H]+: 327.1320. Found: 327.1305.

1. customThe compound was purified by preparative HPLC (2 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm)
2. custombuffer over 20 minutes
3. additionThe product containing fractions
4. customdried
5. additionagain treated with hydrogen bromide
6. customThe compound was purified by preparative HPLC (3 equal injections) on a XBridge C18 column (10 μm 250×50 ID mm)
7. custombuffer over 20 minutes