4-Chloro-2-fluoro-1-nitrobenzene → 1-Carbethoxy-4-(5-chloro-2-nitroanilino)-piperidine

Participants

Reaction Steps

To a solution of 2.03 g (11.6 mmol) of 4-chloro-2-fluoro-nitrobenzene in DMF (12.0 mL) at rt was added 2.00 g (11.6 mmol) of ethyl 4-amino-1-piperidinecarboxylate. A yellow precipitate formed within 30 min and the reaction was further diluted with DMF (12.0 mL) and CH2Cl2 (5.0 mL) and was shaken at 300 RPM overnight. The solvent was removed under reduced pressure and the resulting solid was dried under vacuum. The crude product was purified by flash chromatography (silica, 0-5% MeOH/CH2Cl2) to afford 2.83 g (81%) of the title compound. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.4. MS (electrospray): m/z calculated for C14H18ClN3O4 [M++Na] 350.09, observed 350.0. 1H NMR (400 MHz, CDCl3): 8.13 (apparent d, J=9.1 Hz, 2H), 6.84 (d, J=2.0 Hz, 1H), 6.62 (dd, J=9.4, 2.3 Hz, 1H), 4.15 (q, J=14.9, 7.3 Hz, 2H), 4.08 (br d, J=12.4 Hz, 2H), 3.70-3.58 (m, 1H), 3.17-3.05 (m, 2H), 2.07 (br dd, J=13.1, 3.1 Hz, 2H), 1.63-1.50 (m, 2H), 1.28 (t, J=7.0 Hz, 3H).

Provenance & Evidence