4-nitro-3-(piperidin-1-yl)benzoic acid synthesis

Yield:1141473-72-4 91%

Reaction Conditions:

in ethanol at 20; for 24 h;

Steps:

18

3-Fluoro-4-nitrobenzoic acid (Combi-Blocks CA-4022, 5 g; 27.01 mmol) was dissolved in EtOH (30 mL) to which was added piperidine (8.02 mL; 81.03 mmol). The reaction mixture was stirred at RT for 24 hours, then concentrated and the residue was taken up in water (300 mL). The aqueous phase was washed with Et₂O then the aqueous phase was acidified with acetic acid until pH 5. The aqueous phase was extracted with Et₂O (900 mL). The combined organic phases were dried over MgSO₄ and concentrated affording the title compound as an orange solid (6.18 g, 91 %). ¹H NMR (DMSO-d₆, 300 MHz) δ 13.55 (br s, 1 H), 7.89-7.86 (d, J = 8.42 Hz, 1 H), 7.77-7.76 (d, J = 1.40 Hz, 1 H), 7.60-7.57 (dd, J = 8.42 Hz, 1.50 Hz, 1 H), 3.23-2.98 (m, 2H), 3.21 -3.05 (m, 4H), 1.63-1 .58 (m, 6H). HPLC (Method A) Rt 3.88 min (Purity: 99.9%).

References:

WO2009/43889,2009,A2 Location in patent:Page/Page column 124