Phosphorus oxychloride → 2-Chloro-4,6-dimethyl-3-nitropyridine

Temperature

95 °C

A mixture of 4,6-dimethyl-3-nitro-2(1H)-pyridinone (step 1, 10.0 g, 29.7 mmol) in phosphorus oxychloride (35 mL, 187.3 mmol) was stirred at 95° C. for 3 h, then cooled to 45° C. The excess amount of phosphorus oxychloride was removed by distillation under reduced pressure at 45° C. The residue was cooled to room temperature, and diluted with dichloromethane (75 mL). The resulting solution was cooled to 0° C., and 2N hydrochloric acid (50 mL) was added dropwise into the solution. The organic layer was separated, and washed with 2N hydrochloric acid (4×25 mL), 2N aqueous NaOH (2×50 mL) and brine (50 mL). The organic phase was dried (MgSO4) and concentrated under reduced pressure to give 10.0 g (90%) of the title compound as white solids: 1H-NMR (CDCl3) δ 7.07 (1H, s), 2.56 (3H, s), 2.35 (3H, s).

1. temperaturecooled to 45° C
2. customThe excess amount of phosphorus oxychloride was removed by distillation under reduced pressure at 45° C
3. temperatureThe residue was cooled to room temperature
4. additiondiluted with dichloromethane (75 mL)
5. temperatureThe resulting solution was cooled to 0° C.
6. addition2N hydrochloric acid (50 mL) was added dropwise into the solution
7. customThe organic layer was separated
8. washwashed with 2N hydrochloric acid (4×25 mL), 2N aqueous NaOH (2×50 mL) and brine (50 mL)
9. dry with materialThe organic phase was dried (MgSO4)
10. concentrationconcentrated under reduced pressure

ORD record

ord-9b2b522eea0a42cdb855ee1356d4f0d6

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07148234B2