Réaction #306999

Équation de réaction

ethyl 4-fluoro-3-nitrobenzoate

2-methylpiperidine

lithium hydroxide

→

title compound

Rendement 80.0%

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

Rendement 80.0%

Solvants

THF

DMF

water

Conditions de réaction

Traitement

1. 1
   Températureto cool to RT
2. 2
   ExtractionExtraction with EtOAc
3. 3
   Séchagedrying over sodium sulfate and concentration under vacuum
4. 4
   Autregave a yellow oil that
5. 5
   AutreAfter evaporation of the THF
6. 6
   workup.ADDITIONthe solution was diluted with water
7. 7
   Lavagewashed with Et2O
8. 8
   Extractionextracted with Et2O
9. 9
   Séchagedried over MgSO4
10. 10
    Concentrationconcentrated under vacuum

Mode opératoire

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%).

Source