Hydrochloric Acid → 4-Methoxy-6-methylpyridin-2-amine
Reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.[CH3:10][O-:11].[Na+].Cl>>[CH3:10][O:11][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=1Participants
4
Conditions
- Temperature
- 130 °C
Procedure
To 4-chloro-6-methylpyridin-2-amine (1.0 g, 7.0 mmol) was added sodium methoxide (25% solution in methanol, 9.2 ml, 35 mmol) under a nitrogen atmosphere. The reaction mixture was heated in a microwave at 130° C. for 12 hours. The reaction mixture was quenched with hydrochloric acid (1.0 M in water, 42 ml, 42 mmol), and the reaction mixture was partially concentrated under reduced pressure to remove methanol. The residue was diluted with ethyl acetate, and the pH was adjusted to ˜7.5 with saturated aqueous sodium bicarbonate solution. The organics were separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (dichloromethane/methanol with ammonium hydroxide, linear gradient) to afford 4-methoxy-6-methylpyridin-2-amine. MS ESI calc'd. for C7H11N2O [M+H]+ 139. found 139. 1H NMR (500 MHz, DMSO-d6) δ 5.96 (d, J=1.5 Hz, 1H), 5.75 (d, J=2.0 Hz, 1H), 5.70 (br s, 2H), 3.66 (s, 3H), 2.13 (s, 3H).