Sodium Acetate → 3-(Aminomethyl)-5-fluoro-4,6-dimethyl-2(1H)-pyridinone

Participants

Reaction Steps

5-Fluoro-4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (1.0 g, 6.02 mmol) was suspended in 50 mL of HOAc at room temperature to give a dark brownish solution. NaOAc (1.0 g, 12.3 mmol, 2 equiv), PtO2 (20 mg) and 5% Pd/C (1.3 g) were charged into a 500 mL Parr bottle, followed by wetting with some acetic acid under nitrogen. The substrate solution was then added, and rinsed with another 50 mL of acetic acid. The mixture was hydrogenated under a pressure of 40 psi. There was initial drop of hydrogen pressure and the vessel was refilled. The mixture was hydroganted for 6 h. The mixture was filtered through Celite, and concentrated in vacuo to give a solid residue, which was suspended in 6 mL of conc. HCl to give a paste. The paste was filtered, and the cake was washed with 1 mL of conc HCl (in duplicate). The filtrate was concentrated in vacuo. The solid residue dissolved in 0.4 mL of conc. HCl and 6 mL of EtOH as a suspension, which was stored in the freezer for 2 h, followed by filtration. The cake was washed with 2 mL of cold EtOH (in duplicate). The solids were dried under vacuum at room temperature for 18 h to give the title compound as a cream-colored solid (1.03 g). LC-MS (ES) m/z=171 [M+H]+ and a dominant peak at 154. 1H NMR (400 MHz, DMSO-d6) δ ppm, 2.20 (d, J=3.0 Hz, 3 H), 2.22 (d, J=2.0 Hz, 3 H), 3.83 (q, J=5.2 Hz, 2 H), 7.99 (br. s., 3 H), 11.99 (br. s., 1 H).

Provenance & Evidence