p-Toluenesulfonic acid monohydrate → HCID 67065996, compound

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 1-benzyl-4-(2-fluoro-4-methoxyphenyl)piperidin-4-ol (Step A; 300 mg; 0.952 mmol) and p-toluenesulfonic acid monohydrate (18 mg; 0.0952 mmol) in benzene (20 mL) was heated at 80° C. for 14 h. An additional 100 mg of p-toluenesulfonic acid monohydrate was added and the reaction heated at 80° C. for 1 h. The reaction was partitioned between EtOAc (50 mL) and H2O (50 mL). The aqueous layer was extracted with EtOAc (3×50 mL) and the combined extracts were washed with H2O (3×50 mL) and brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient) to afford 1-benzyl-4-(2-fluoro-4-methoxyphenyl)1,2,3,6-tetrahydropyridine as a yellow oil. LCMS=297.9 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 9.56 (br s, 1H), 7.42-7.38 (m, 2H), 7.34 (t, J=7.3 Hz, 2H), 7.28 (d, J=7.3 Hz, 1H), 7.17 (t, J=8.7 Hz, 1H), 6.64 (dd, J=8.7, 2.5 Hz, 1H), 6.59 (dd, J=13.0, 2.5 Hz, 1H), 5.91-5.89 (m, 1H), 3.78 (s, 3H), 3.66 (br s, 2H), 3.18 (br s, 2H), 2.71 (br s, 2H), 2.54 (br s, 2H).

Provenance & Evidence