Acetic Acid → N-(2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethyl)-3,3,3-trifluoro-2,2-dim ethylpropan-1-amine

Participants

Reaction Steps

To a yellow clear mixture of 2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethanamine (3.57 g, 11.11 mmol) in DCM (37.0 mL) was added 3,3,3-trifluoro-2,2-dimethylpropanal (11.11 mmol) in DCM followed by AcOH (0.770 ml, 13.33 mmol) and NaBH(OAc)3 (3.53 g, 16.67 mmol). The yellow heterogeneous mixture was stirred at room temperature. After 8 h, the mixture was quenched with saturated NaHCO3 (100 mL). The reaction mixture was extracted with DCM (2×100 mL). The organic extract was dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as orange syrup. 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 20% EtOAc in heptane to provide N-(2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethyl)-3,3,3-trifluoro-2,2-dim ethylpropan-1-amine (A294) (3.4393 g, 7.72 mmol, 69.5% yield) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.44 (2H, s), 5.48 (1H, dd, J=7.7, 4.4 Hz), 3.27 (1H, dd, J=12.3, 8.4 Hz), 2.58-2.83 (3H, m), 1.25-1.44 (1H, m), 1.10 (6H, s), 0.85-0.94 (9H, m), 0.47-0.64 (6H, m); LCMS (ESI) m/z 445.1 (M+H)+.

Provenance & Evidence