Phosphorus oxychloride → 2-Chloro-4-methoxypyridine

4-Methoxy-2-pyridone (10) (0.805 g, 6.43 mmol) and freshly distilled POCl3 (8 mL) were heated at reflux for 15 h. Excess POCl3 was removed in vacuo and the resultant viscous oil was cooled in ice and carefully neutralised with saturated NaHCO3 solution. The mixture was extracted with EtOAc (×3) and the extracts were worked up in the standard manner to give a brown oil. This material was partially purified by vacuum distillation in a Kugelrohr apparatus (100° C., 0.07 mm Hg). The distillate was triturated with petroleum ether and a white precipitate was filtered off. The filtrate was concentrated and final purification by flash chromatography on silica gel using 30% EtOAc/hexanes as the eluant gave 2-chloro-4-methoxypyridine (11) as a colourless oil (0.586 g, 63%).

1. temperatureat reflux for 15 h
2. customExcess POCl3 was removed in vacuo
3. temperaturethe resultant viscous oil was cooled in ice
4. extractionThe mixture was extracted with EtOAc (×3)
5. customto give a brown oil
6. distillationThis material was partially purified by vacuum distillation in a Kugelrohr apparatus (100° C., 0.07 mm Hg)
7. distillationThe distillate was triturated with petroleum ether
8. filtrationa white precipitate was filtered off
9. concentrationThe filtrate was concentrated
10. customfinal purification by flash chromatography on silica gel using 30% EtOAc/hexanes as the eluant

ORD record

ord-8863f36082f744609816e1fc81ebd4a5

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07320981B2