4-Aminomethyltetrahydropyran → N-methyl-N-{3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}acetamide

Participants

Reaction Steps

4-Aminomethyltetrahydropyran (10.0 g, 86.5 mmol) was added to a mixture of N-(4-fluoro-3-nitrophenyl)-N-methylacetamide (15.6 g, 73.3 mmol) and TEA (15.3 mL, 11.1 g, 110 mmol) in EtOH (300 mL) at room temperature. The reaction mixture was heated for 6 h at reflux. Upon evaporation of ethanol, the residue was dissolved in EtOAc (400 mL), washed with H2O (3×50 mL), saturated NaCl (3×50 mL), and dried over Na2SO4. After filtration and concentration, 21.7 g (96%) of the title compound was obtained as an orange-red solid. 1H NMR (400 MHz, CHLOROFORM-D): δ 1.38-1.52 (m, 2 H), 1.72-1.81 (m, 2 H), 1.90 (s, 3 H), 1.93-2.02 (m, 1 H), 3.23 (s, 3 H), 3.23-3.27 (m, 2 H), 3.36-3.49 (m, 2 H), 4.01-4.07 (m, 2 H), 6.91 (d, J=9.18 Hz, 1 H), 7.29 (dd, J=9.08, 2.64 Hz, 1 H), 8.05 (d, J=2.34 Hz, 1 H), 8.22 (t, J=5.37 Hz, 1 H). MS (ESI) (M+H)+=309.12.

Provenance & Evidence