Cesium carbonate → tert-Butyl 4-{[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]oxy}piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

2-Bromo-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (2.7 g, 7.51 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (1.5 g, 7.51 mmol), palladium(II) acetate (0.034 g, 0.15 mmol), biphenyl-2-yl(di-tert-butyl)phosphine (0.056 g, 0.19 mmol) and cesium carbonate (4.9 g, 15.0 mmol) were mixed in a 40 mL vial and dry toluene (25 ml) was added. The vial was then briefly evacuated and backfilled with N2 five times, and the reaction vessel was heated at 100° C. under N2 atmosphere for 24 hours. The reaction mixture was cooled to room temperature. The reaction mixture was diluted with toluene (100 mL), washed with water, the organics dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography using a gradient with toluene:EtOAc (98:2-80:20), gave the product as an oil. Yield: 1.1 g (33%). 1H NMR (400 MHz, CDCl3) δ 7.44 (t, 1H, J=7.82 Hz), 6.89 (d, 1H, J=7.30 Hz), 6.43 (d, 1H, J=8.34 Hz), 5.04-5.11 (m, 1H), 4.56 (s, 2H), 3.58-3.68 (m, 2H), 3.12-3.21 (m, 2H), 1.78-1.87 (m, 2H), 1.53-1.64 (m, 2H), 1.35 (s, 9H), 0.84 (s, 9H), 0.00 (s, 6H). MS (ESI+) 423.24 (M+1H+).

Provenance & Evidence