反应详情

温度

2.5 °C

To a solution of (R)-5-((tert-butyldiphenylsilyl)oxy)hexan-1-ol (8.23 g, 23.08 mmol) and tert-butyl 4-methylenepiperidine-1-carboxylate (6.83 g, 34.6 mmol) in CH2Cl2 (40 mL) was added TMS-OTf (0.334 mL, 1.846 mmol), followed by CuSO4 (1.842 g, 11.54 mmol) and the slurry was cooled to 0-5° C. N-iodosuccinimide (7.79 g, 34.6 mmol) was then added in one portion and the slurry was stirred for 0-5° C. for additional 16 h, then warmed to room temp over 2-3 h. Ether (200 mL) followed by aqueous solution of Na2S2O3 (5% 100 mL) was added and the layers were separated. Organic layer was then washed with water (100 mL), dried (Na2SO4), filtered and concentrated. The residue was then purified by column chromatography (EtOAc/hexanes, 5-20%) to afford (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate (13 g, 15.30 mmol, 66.3% yield) as yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.70 (dt, J=7.1, 1.7 Hz, 4H), 7.47-7.36 (m, 6H), 3.93 (s, 1H), 3.91-3.69 (m, 2H), 3.25 (br. s., 2H), 3.20 (t, J=6.4 Hz, 2H), 3.00 (br. s., 2H), 1.87 (d, J=13.1 Hz, 2H), 1.57-1.50 (m, 4H), 1.48 (s, 9H), 1.45-1.35 (m, 4H), 1.15-1.02 (m, 12H). LCMS (M-BOc)=580.6.

1. temperaturewarmed to room temp over 2-3 h
2. additionwas added
3. customthe layers were separated
4. washOrganic layer was then washed with water (100 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was then purified by column chromatography (EtOAc/hexanes, 5-20%)