Reacción #306999

Ecuación de reacción

ethyl 4-fluoro-3-nitrobenzoate

2-methylpiperidine

lithium hydroxide

→

title compound

Rendimiento 80.0%

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

Rendimiento 80.0%

Disolventes

THF

DMF

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato cool to RT
2. 2
   ExtracciónExtraction with EtOAc
3. 3
   Secadodrying over sodium sulfate and concentration under vacuum
4. 4
   Otrogave a yellow oil that
5. 5
   OtroAfter evaporation of the THF
6. 6
   workup.ADDITIONthe solution was diluted with water
7. 7
   Lavadowashed with Et2O
8. 8
   Extracciónextracted with Et2O
9. 9
   Secadodried over MgSO4
10. 10
    Concentraciónconcentrated under vacuum

Procedimiento

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%).

Fuente