Water → 1-(2-fluoro-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole

Temperature

80 °C

A mixture of 3-methyl-1H-1,2,4-triazole (15.0 g, 181 mmol), 1,2-difluoro-4-nitrobenzene (28.7 g, 181 mmol), and sodium bicarbonate (15.2 g, 181 mmol) in DMSO (100 mL) was heated at 80° C. for 48 h. The reaction mixture was allowed to cool to rt and was poured into water (800 mL). The aqueous mixture was extracted with EtOAc (3×200 mL). The combined organic extracts were sequentially washed with water (500 mL) and brine solution (100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude reaction mixture was purified using silica gel chromatography (30-80% EtOAc/hexane, linear gradient) to afford two regioisomeric products. Pure fractions of the less polar regioisomer were combined and concentrated to afford 1-(2-fluoro-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole (7.2 g, 30.8 mmol, 17% yield) as an off-white solid. Pure fractions of the more polar regioisomer were combined and concentrated to afford 1-(2-fluoro-4-nitrophenyl)-5-methyl-1H-1,2,4-triazole (6.23 g, 28.0 mmol, 15% yield) as an off-white solid. Data for 1-(2-fluoro-4-nitrophenyl)-5-methyl-1H-1,2,4-triazole: LC-MS (M+H)+=223.1. 1H NMR (500 MHz, CDCl3) δ ppm 8.18-8.24 (m, 2H) 8.04 (s, 1H) 7.69-7.78 (m, 1H) 2.47-2.53 (m, 3H).

1. temperatureto cool to rt
2. extractionThe aqueous mixture was extracted with EtOAc (3×200 mL)
3. washThe combined organic extracts were sequentially washed with water (500 mL) and brine solution (100 mL)
4. dry with materialThe organic layer was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude reaction mixture
8. customwas purified
9. customto afford two regioisomeric products
10. concentrationconcentrated

ORD record

ord-35823e930791438a98731b7091f0a116

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486952B2