Réaction #306984

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

water

Conditions de réaction

Traitement

1. 1
   Températurewas cooled to RT
2. 2
   Extractionextracted with EtOAc
3. 3
   Séchagedried over MgSO4
4. 4
   Concentrationconcentrated
5. 5
   Autregiving a yellow oil
6. 6
   AutreAfter evaporation of THF
7. 7
   workup.ADDITIONthe solution was diluted with water
8. 8
   Lavagewashed with Et2O
9. 9
   Extractionextracted with Et2O
10. 10
    Séchagedried over MgSO4
11. 11
    Concentrationconcentrated

Mode opératoire

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Clontech 01072, 25 g; 117.28 mmol; 1 eq.) and 2-methylpiperidine (41.54 mL; 351.84 mmol; 3 eq.) in DMF (100 mL) was heated to 50° C. for 2 hours The reaction was cooled to RT and diluted with water (100 mL), extracted with EtOAc, dried over MgSO4 and concentrated giving a yellow oil. The residue was taken up in THF (250 mL) and lithium hydroxide (14.04 g; 586.41 mmol; 5 eq.) was added followed by water (250 mL). The reaction mixture was stirred at RT for 2 days. After evaporation of 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 affording the title compound as a yellow solid (24.81 g, 80%). 1H NMR (DMSO-d6, 300 MHz) δ 13.09 (br s, 1H), 8.23-8.22 (d, J=2.14 Hz, 1H), 8.04-8.01 (dd, J=8.72 Hz, 2.19 Hz, 1H), 7.44-7.41 (d, J=8.94 Hz, 1H), 3.63-3.61 (m, 1H), 3.22-3.18 (m, 1H), 2.89-2.85 (m, 1H), 1.78-1.44 (m, 6H), 1.06-1.04 (d, J=6.65 Hz, 3H). LC/MS (Method B): 265.2 (M+H)+; 263.2 (M+H)−. HPLC (Method A) Rt 3.96 min (Purity: 97.9%)

Source