反应详情

Benzyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate (Intermediate 13; 2.90 g, 6.49 mmol) and palladium on activated carbon (10%, wet, 600 mg) in ethanol (50 mL) were stirred under an atmosphere of hydrogen (1 atm) at RT for 2 h. The mixture was filtered (glass wool filter paper, Whatman 1821 110), and washed with ethanol. The filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel chromatography (120 g RediSep, eluted with a gradient of dichloromethane/CMA, 9:1, 500 mL; 4:1, 1 L; 7:3, 3 L provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.90 (s, 1H), 7.59 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.12 (t, J=6.7 Hz, 2H), 3.17-3.00 (m, 2H), 2.65-2.45 (m, 2H), 2.25-2.05 (m, 1H), 1.90-1.70 (m, 3H), 1.63-1.47 (m, 1H), 1.43-1.23 (m, 2H), 1.02-0.84 (m, 2H), 0.74-0.57 (m, 2H), −0.12 (q, J=4.3 Hz, 1H). MS (Multimode) m/z 314 [M+H]+.

1. filtrationThe mixture was filtered
2. filtration(glass wool filter paper, Whatman 1821 110)
3. washwashed with ethanol
4. concentrationThe filtrate was concentrated to dryness under reduced pressure
5. customThe residue was purified by silica gel chromatography (120 g RediSep
6. washeluted with a gradient of dichloromethane/CMA, 9:1, 500 mL