4-Bromoanisole → 1-Benzyl-4-(4-methoxyphenyl)piperidin-4-ol

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[Mg].[CH2:11]([N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[CH2:11]([N:18]1[CH2:23][CH2:22][C:21]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)([OH:24])[CH2:20][CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

Procedure

4-Bromoanisole (13 ml, 0.1038 mol) in THF (13.5 ml) is added to a mixture of magnesium (2.24 g, 92.2 mmol) in dry THF (20 ml). When the magnesium is consumed the reagent mixture (XIII) is cooled in a ice/water bath and a mixture of 1-benzyl-4-piperidone (XII, 15 ml, 80.9 mmol) in THF (35 ml) is added dropwise over 21 minutes. The bath is then removed and the mixture stirred for 27 minutes, then poured into saturated aqueous sodium bicarbonate. The mixture is extracted several times with ether and the combined organic extracts are dried over magnesium sulfate, concentrated and the resulting material chromatographed on silica gel eluting with methanol/dichloromethane (4/96) containing ammonium hydroxide (0.4%). Impure fractions are combined and rechromatographed as above to give 1-benzyl-4-(4-methoxyphenyl)piperidin-4-ol (XIV), NMR (CDCl3) 1.74, 2.14, 2.46, 2.78, 3.58, 3.80, 6.88, 7.31 and 7.44 δ.