Nitrogen → 1-(5-bromopyridin-2-yl)-N,N-dimethylpiperidin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a 100 mL single-necked round-bottom flask were placed 2,5-dibromopyridine (2 g, 8 mmol), 4-(dimethylamino)piperidine (1 ml, 8 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.07 g, 0.08 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.1 g, 0.2 mmol), and sodium t-butoxide (1 g, 12 mmol). The flask was subjected to 3 cycles of evacuation and back-filling with N2 before toluene (40 mL) was introduced under N2. The resulting mixture was stirred at a preheated oil bath at 100° C. for 40 min. The crude mixture was poured into ice and 4 N NaOH aqueous solution and extracted with ethyl acetate (2×). The combine organics were dried over sodium sulfate and concentrated in vacuo to give 2.7 g crude product. Trituration with ethyl acetate/hexanes gave highly pure 1-(5-bromopyridin-2-yl)-N,N-dimethylpiperidin-4-amine (91) (1.9 g, 95%) 1H NMR (400 MHz, CDCl3) δ 8.18 (1 H, d, J=2.3 Hz), 7.52 (1 H, dd, J=9.0, 2.7 Hz), 6.58 (1 H, d, J=9.0 Hz), 4.30 (2 H, d, J=12.9 Hz), 2.79-2.91 (2 H, m), 2.49 (1 H, br. s.), 2.37 (6 H, s), 1.97 (2 H, d, J=12.5 Hz), 1.45-1.60 (2 H, m) ppm.

Provenance & Evidence