Hydrochloric Acid → 3,4-Dichloro-2-methoxypyridine

Temperature

-5 °C

3-Amino-4-chloro-2-methoxypyridine (200 mg, 1.27 mmol), dissolved in conc. hydrochloric acid (4 mL) was stirred at −5° C. while a solution of sodium nitrite (437 mg, 6.33 mmol) in water (2 mL) was added dropwise over 10 min. The mixture was stirred for a further 10 min before copper chloride (1.25 g, 12.66 mmol) was added portionwise over 5 min. The dark effervescing mixture was stirred at −5° C. for 20 min and then the cooling bath was removed and the mixture stirred at ambient temperature for 1 h. The resultant green solution was basified by addition of 5N sodium hydroxide (aq.), diluted with water (100 mL) and extracted with diethyl ether (3×30 mL). The combined extracts were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound (218 mg, 97%).

1. additionwas added dropwise over 10 min
2. additionwas added portionwise over 5 min
3. customthe cooling bath was removed
4. stirringthe mixture stirred at ambient temperature for 1 h
5. additionThe resultant green solution was basified by addition of 5N sodium hydroxide (aq.)
6. additiondiluted with water (100 mL)
7. extractionextracted with diethyl ether (3×30 mL)
8. washThe combined extracts were washed with brine (50 mL)
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo

ORD record

ord-066b773aea534e2f96593271726aee1d

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07868017B2