Ammonium Chloride → 6-Chloro-5-methylpyridin-3-amine

Reduced iron (793 mg) was added to an aqueous solution (25 mL) of ammonium chloride (1.27 g), and the mixture was stirred at room temperature for 5 min. A solution (10 mL) of 2-chloro-3-methyl-5-nitropyridine (816 mg) in methanol was added dropwise over 10 min. The reaction mixture was stirred at 40° C. for 20 min and at 50° C. for 1.5 hr and further refluxed under heating for 1 hr. The reaction mixture was filtered through celite, and celite was washed with methanol. Methanol was mostly removed by concentrated under reduced pressure, and saturated aqueous sodium hydrogencarbonate solution was added. The mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→7:3) to give the title compound as a solid (yield 280 mg, 42%).

1. stirringThe reaction mixture was stirred at 40° C. for 20 min and at 50° C. for 1.5 hr
2. temperaturefurther refluxed
3. temperatureunder heating for 1 hr
4. filtrationThe reaction mixture was filtered through celite, and celite
5. washwas washed with methanol
6. customMethanol was mostly removed
7. concentrationby concentrated under reduced pressure, and saturated aqueous sodium hydrogencarbonate solution
8. additionwas added
9. extractionThe mixture was extracted with ethyl acetate
10. washThe extract was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→7:3)

ORD record

ord-158b7943e323415384af0a1a5caeff78

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08048909B2