反応 #306999

反応方程式

ethyl 4-fluoro-3-nitrobenzoate

2-methylpiperidine

lithium hydroxide

→

title compound

収率 80.0%

4-(2-methylpiperidin-1-yl)-3-nitrobenzoic acid

収率 80.0%

溶媒

THF

DMF

water

反応条件

後処理

1. 1
   温度to cool to RT
2. 2
   抽出Extraction with EtOAc
3. 3
   乾燥drying over sodium sulfate and concentration under vacuum
4. 4
   その他gave a yellow oil that
5. 5
   その他After evaporation of the THF
6. 6
   workup.ADDITIONthe solution was diluted with water
7. 7
   洗浄washed with Et2O
8. 8
   抽出extracted with Et2O
9. 9
   乾燥dried over MgSO4
10. 10
    濃縮concentrated under vacuum

実験手順

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%).

出典