反应详情

温度

50 °C

A mixture of ethyl 4-fluoro-3-nitrobenzoate (25 g; 117.28 mmol) and 2-methylpiperidine (41.54 mL; 351.84 mmol) in DMF (100 mL) was heated to 50° C. for 2 h. The reaction was allowed to cool to RT and diluted with water (100 mL). Extraction with EtOAc, drying over sodium sulfate and concentration under vacuum gave a yellow oil that was taken up in THF (250 mL) followed by the addition of an aqueous solution of lithium hydroxide (14.0 g; 586.4 mmol, 2.3 M). The reaction mixture was stirred at RT for 48 h. After evaporation of the THF, the solution was diluted with water and washed with Et2O. The aqueous layer was acidified to pH 5 with AcOH, extracted with Et2O, dried over MgSO4 and concentrated under vacuum to give the title compound as a yellow solid (24.8 g, 80%). 1H NMR (DMSO-d6, 300 MHz) δ 13.1 (bs, 1H), 8.23 (d, J=2 Hz, 1H), 8.02 (dd, J=8.7, 2 Hz, 1H), 7.41 (d, J=8.7 Hz, 1H), 3.63-3.61 (m, 1H), 3.23-3.18 (m, 1H), 2.89-2.85 (m, 1H), 1.79-1.54 (m, 6H), 1.47 (d, J=6 Hz, 3H). LC/MS (Method B): 265.2 (M+H)+. HPLC (Method A) Rt 3.96 min (Purity: 97.9%).

1. temperatureto cool to RT
2. extractionExtraction with EtOAc
3. dry with materialdrying over sodium sulfate and concentration under vacuum
4. customgave a yellow oil that
5. customAfter evaporation of the THF
6. additionthe solution was diluted with water
7. washwashed with Et2O
8. extractionextracted with Et2O
9. dry with materialdried over MgSO4
10. concentrationconcentrated under vacuum