3-Bromoanisole → 1-Benzyl-3-(3-methoxyphenyl)piperidin-3-ol

Participants

Reaction Conditions

Reaction Steps

To a suspension of magnesium (7.8 g, 325 mmol) in THF (120 mL) at room temperature under a nitrogen atmosphere was added a solution of 3-bromoanisole (37.5 mL, 296 mmol) in THF (60 mL) over 10 min. The resulting mixture was stirred at 50° C. for 4 hours and was cooled to room temperature. To the mixture was added a solution an N-benzyl-3-piperidinone (30.0 g, 159 mmol) in THF (50 mL). The reaction was stirred at room for 10 hours. The mixture was poured slowly over ice-water (100 mL) and the aqueous layer was washed with EtOAc (3×50 mL). The combined organic extracts were dried (MgSO4) and concentrated. The crude residue was purified by flash chromatography with hexanes/EtOAc (3:1) to afford 38.4 g of 1-benzyl-3-(3-methoxy-phenyl)-piperidin-3-ol 1HNMR (400 MHz, CDCl3) δ 7.31-7.20 (comp, 6H), 7.09 (s, 1H), 7.01 (d, 1H), 6.79 (d, 1H), 4.01-3.96 (br, 1H), 3.79 (s, 3H), 3.58 (s, 2H), 2.91 (d, 1H), 2.74 (d, 1H), 2.32 (d, 1H), 2.09-1.82 (comp, 2H), 1.81-1.61 (comp, 3H); MS (M+1) 298.2.

Provenance & Evidence