반응 #306999

반응 방정식

ethyl 4-fluoro-3-nitrobenzoate

2-methylpiperidine

lithium hydroxide

→

title compound

수율 80.0%

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

수율 80.0%

용매

THF

DMF

water

반응 조건

후처리

1. 1
   온도to cool to RT
2. 2
   추출Extraction with EtOAc
3. 3
   건조drying over sodium sulfate and concentration under vacuum
4. 4
   기타gave a yellow oil that
5. 5
   기타After evaporation of the THF
6. 6
   workup.ADDITIONthe solution was diluted with water
7. 7
   세척washed with Et2O
8. 8
   추출extracted with Et2O
9. 9
   건조dried over MgSO4
10. 10
    농축concentrated under vacuum

실험 절차

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%).

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