反应详情

3-Nitro-5-trifluoromethyl-pyridine-2-carbonitrile (6.5 g, 29.9 mmol) was dissolved in EtOAc (150 ml) to give a pale yellow solution and placed under an atmosphere of nitrogen. 10% Palladium on activated carbon (3.19 g, 2.99 mmol) was added and the reaction mixture stirred under an atmosphere of hydrogen for 18 hours. The reaction mixture was filtered and concentrated in vacuo. The crude residue was dissolved in HCl conc. (45 ml) and heated to reflux for 24 hours. The reaction mixture was allowed to cool to RT and concentrated in vacuo. The solid was dissolved in MeOH (300 ml) and sulfuric acid (14.4 ml) was added. The resulting solution was heated at reflux for 48 hours. The reaction was allowed to cool to RT, then neutralised by addition of 10% NaHCO3(aq) (600 ml). The product was extracted into DCM (3×200 ml) and the combined organic phases were washed with water (200 ml), brine (50 ml), (MgSO4) and concentrated in vacuo. The resulting solid was purified by chromatography on silica: Eluant gradient: isohexane (500 ml), 10% EtOAc in isohexane (1000 ml), 20% EtOAc in isohexane (1500 ml) to afford the titled compound as a pale yellow solid 1H-NMR: [400 MHz, DMSO-d6, δH 8.13 (1H, d, J=1.7 Hz, ArH), 7.60 (1H, d, J=1.3 Hz, ArH), 7.01 (2H, br, NH2), 3.85 (3H, s, ArOCH3), m/z 221.1 [M+H]+

1. customto give a pale yellow solution
2. filtrationThe reaction mixture was filtered
3. concentrationconcentrated in vacuo
4. dissolutionThe crude residue was dissolved in HCl conc. (45 ml)
5. temperatureheated
6. temperatureto reflux for 24 hours
7. concentrationconcentrated in vacuo
8. dissolutionThe solid was dissolved in MeOH (300 ml)
9. additionsulfuric acid (14.4 ml) was added
10. temperatureThe resulting solution was heated
11. temperatureat reflux for 48 hours
12. temperatureto cool to RT
13. additionneutralised by addition of 10% NaHCO3(aq) (600 ml)
14. extractionThe product was extracted into DCM (3×200 ml)
15. washthe combined organic phases were washed with water (200 ml), brine (50 ml), (MgSO4)
16. concentrationconcentrated in vacuo
17. customThe resulting solid was purified by chromatography on silica