N-Methoxy-N-methylacetamide → Ethanone, 1-(2-chloro-8-quinolinyl)-

Participants

Reaction Steps

To a solution of 8-bromo-2-chloroquinoline (Biofine International, Vancouver, BC; 10.0 g, 41.2 mmol) in 200 mL THF in a dry ice/acetone bath was added nBuLi solution (2.5 M in hexanes; 18.14 ml, 45.4 mmol) slowly (dropwise) via addition funnel such that the internal temperature did not exceed −72° C. After 15 min, N-methoxy-N-methylacetamide (Aldrich; 5.05 ml, 49.5 mmol) was added via syringe such that the internal temperature did not exceed −72° C. The dry ice/acetone bath was removed and the reaction was quenched with 200 mL saturated aq. NH4Cl and diluted with 300 mL Et2O. The organic layer was washed 1× brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (240 g column) using 0-20% EtOAc/hexanes until less polar impurities elute, then 20-40% EtOAc/hexanes to elute desired material. Fractions were combined and concentrated to give 1-(2-chloroquinolin-8-yl)ethanone (3.63 g, 17.65 mmol, 43% yield) as a peach-colored solid: 1H NMR (400 MHz, CDCl3) δ ppm 8.16 (1H, d, J=8.6 Hz), 8.06 (1H, dd, J=7.2, 1.6 Hz), 7.96 (1H, dd, J=8.0, 1.6 Hz), 7.59-7.66 (1H, m), 7.46 (1H, d, J=8.6 Hz), 2.98 (3H, s). m/z (ESI, +ve) 206.0 (M+H)+.

Provenance & Evidence