Sodium hydride → 2-Methoxy-3,6-dimethyl-5-nitropyridine

Temperature

70 °C

Dimethyl sulfoxide (35 mL) was added to a dry round-bottomed flask containing NaH (1.82 g, 45.5 mmol, 60% in mineral oil). The resulting suspension was heated at 70° C. for 35 min during which time the suspension became a solution. The reaction mixture was cooled to room temperature, trimethylsulfoxonium iodide (10.0 g, 45.5 mmol) was added, and the mixture was stirred at room temperature for 30 min. 2-Methoxy-3-methyl-5-nitropyridine (4.50 g, 26.80 mmol) from Example 1 Part I, was added and the resulting dark red solution was stirred at room temperature for 30 min, at which time TLC showed complete consumption of starting material. The reaction mixture was transferred to a separatory funnel containing water (30 mL), and the aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (20% ethyl acetate in hexanes) to afford 2-methoxy-3,6-dimethyl-5-nitropyridine (2.00 g, 41% yield) as a colorless solid: mp 85.5-86.2° C.; 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 4.02 (s, 3H), 2.77 (s, 3H), 2.20 (s, 3H).

1. temperatureThe reaction mixture was cooled to room temperature
2. stirringthe resulting dark red solution was stirred at room temperature for 30 min, at which time TLC
3. customconsumption of starting material
4. customThe reaction mixture was transferred to a separatory funnel
5. additioncontaining water (30 mL)
6. extractionthe aqueous layer was extracted with EtOAc (3×100 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by column chromatography on silica gel (20% ethyl acetate in hexanes)

ORD record

ord-db817d733d4442bc9e1b5793784694e9

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436000B2