Sodium Thiosulfate → (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence