Acetic Acid → 2-(3,5-dichloropyridin-4-yl)-N-((5-methyltetrahydrofuran-2-yl)methyl)-2-((triethylsilyl)oxy)ethanamine

Participants

Reaction Steps

To a clear solution of 5-methyltetrahydrofuran-2-methanol in DCM was added Dess-Martin periodinane (1.2 eq.). The mixture was stirred at room temperature overnight. The crude mixture was directly added to a solution of 2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethanamine (1 eq.) in DCM followed by AcOH (1.2 eq.) and NaBH(OAc)3 (1.5 eq.). The reaction mixture was stirred at room temperature. After 2 h, the mixture was quenched with saturated aqueous Na2S2O3 and saturated NaHCO3. The reaction mixture was extracted with DCM. The organic extract was dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was absorbed onto a plug of silica gel and purified by silica gel column chromatography eluting with a gradient of 0% to 25% EtOAc in heptane to provide 2-(3,5-dichloropyridin-4-yl)-N-((5-methyltetrahydrofuran-2-yl)methyl)-2-((triethylsilyl)oxy)ethanamine (A281) as a light-yellow syrup. 1H NMR (300 MHz, DMSO-d6) δ 8.58 (2H, s), 5.34-5.46 (1H, m), 3.71-3.90 (2H, m), 3.10 (1H, dt, J=12.5, 8.1 Hz), 2.90 (1H, td, J=12.1, 6.0 Hz), 2.52-2.67 (2H, m), 1.71-2.07 (3H, m), 1.47-1.64 (1H, m), 1.19-1.38 (1H, m), 1.11 (3H, t, J=6.3 Hz), 0.77-0.89 (9H, m), 0.40-0.62 (6H, m); LCMS (ESI) m/z 419.1 (M+H)+.

Provenance & Evidence