Hydrogen Peroxide → 8-Hydroxy-2-phenyl-5,6,7,8-tetrahydroquinoline

Participants

Reaction Steps

To a stirred solution of 2-phenyl-5,6,7,8-tetrahydroquinoline (3.80 g, 18 mmol) in glacial acetic acid (10 mL) was added a 30 wt. % aqueous solution of H2O2 (2 mL) and the resulting mixture was stirred at 70° for 18 h; at this point, another portion of H2O2 solution (2 mL) was added and stirring was continued for 2 days. The solution was cooled to room temperature and Na2CO3 (10 g) and CHCl3 (20 mL) were added. The resulting mixture was allowed to sit 15 min then filtered and the aqueous phase was extracted with CHCl3 (3×20 mL); the organic fractions were then combined, dried (MgSO4) and concentrated. The residue was then taken up in acetic anhydride (20 mL) and heated at 90° C. for 4 h with stirring. Removal of the Ac2O under reduced pressure afforded a pale yellow oil which was taken up in methanol (30 mL) and treated with K2CO3 (100 mg, 0.72 mmol). The resulting mixture was stirred overnight. A solution of 4 N NaOH (10 mL) was added and the mixture was extracted with CHCl3 (3×20 mL), dried (MgSO4) and concentrated in vacuo. Purification of the crude product by column chromatography (silica gel, hexane/EtOAc 4:1) afforded 3.0 g of 8-hydroxy-2-phenyl-5,6,7,8-tetrahydroquinoline AMD 8786 (74% yield) as a white solid. 1H NMR (CDCl3) δ 1.78–1.81 (m, 2H), 1.97–2.02 (m, 1H), 2.31–2.33 (m, 1H), 2.76–2.79 (m, 2H), 4.43 (s, 1H), 4.71 (t, 1H, J=7 Hz), 7.37–7.46 (m, 4H), 7.52 (d, 1H, J=8 Hz), 7.96 (dd, 2H, J=9, 2 Hz); 13C NMR (CDCl3) δ 19.4, 27.8, 30.5, 69.0, 119.0, 126.5, 128.5, 128.7, 129.8, 137.6, 138.7, 154.0, 157.5. ES-MS m/z 226 (M+H).

Provenance & Evidence