反应详情

Sodium hydride (424 mg, 60% dispersion in mineral oil, 10.6 mmol) was added to a solution of benzyl 4-((1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate (1.07 g, 3.53 mmol) in N,N-dimethylformamide (10 mL) under nitrogen at RT. The mixture was stirred for 30 min at RT and 2-bromo-5-(methylsulfonyl)pyridine (1.25 g, 5.30 mmol) was added. The mixture was stirred overnight, diluted with ethyl acetate (100 mL) and water (50 mL), and the layers were separated. The organic layer was washed with brine (2×25 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (40 g RediSep, eluted with a gradient of hexanes to ethyl acetate, 9:1, 200 mL; 4:1, 500 mL; 1:1, 1 L) to provide the title compound as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.71 (dd, J=0.5, 2.5 Hz, 1H), 8.03 (dd, J=2.5, 8.7 Hz, 1H), 7.40-7.28 (m, 5H), 6.84 (dd, J=0.6, 8.7 Hz, 1H), 5.13 (s, 2H), 4.48 (t, J=7.2 Hz, 2H), 4.30-4.10 (m, 2H), 3.07 (s, 3H), 2.90-2.60 (m, 2H), 2.20-2.00 (m, 1H), 1.85-1.65 (m, 2H), 1.60-1.45 (m, 1H), 1.45-1.20 (m, 2H), 1.10-0.85 (m, 2H), 0.75-0.50 (m, 2H), −0.12 (q, J=5.1 Hz, 1H). MS (Multimode) m/z 459 [M+H]+.

1. stirringThe mixture was stirred overnight
2. customthe layers were separated
3. washThe organic layer was washed with brine (2×25 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography (40 g RediSep
8. washeluted with a gradient of hexanes to ethyl acetate, 9:1, 200 mL