Methanol → 8-Fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinoline

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 8-fluoro-6-nitro-1,2,3,4-tetrahydroquinoline (500 mg, 2.55 mmol) in N,N-dimethylformamide (11 ml), cooled to 0° C. was added sodium hydride, 60% (326 mg, 8.16 mmol) with vigorous stirring. When the bubbling subsided, 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (938 mg, 5.10 mmol) was added and the reaction mixture (dark red) was stirred at 90° C. for 1 h. TLC analysis showed that the reaction mixture was complete. The mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate (3×). The combined organics were then washed with a 1:1 mixture of brine and water (3×), then brine (1×), dried over sodium sulfate, filtered and concentrated. The residue was chromatographed in ethyl acetate, then 10% methanol in 1:1 ethyl acetate:dichloromethane, giving the desired 8-fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinoline (665 mg, 2.164 mmol, 85% yield). 1H NMR (DMSO-d6) δ 7.77 (dd, J=15, 2.7 Hz, 1H), 7.71 (d, J=2.4 Hz, 1H), 3.43-3.32 (m, 4H), 2.94-2.88 (m, 1H), 2.78-2.73 (m, 2H), 2.19 (s, 3H), 2.06-1.97 (m, 2H), 1.91-1.83 (m, 4H); 1.64-1.56 (m, 4H).

Provenance & Evidence