Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[Mg].[C:11]([N:14]1[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]1)(=[O:13])[CH3:12].Cl>O1CCCC1>[OH:20][C:17]1([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)[CH2:18][CH2:19][N:14]([C:11](=[O:13])[CH3:12])[CH2:15][CH2:16]1
4-Bromoanisole (22.4 g, 0.12 mol) in tetrahydrofuran (180 ml) was slowly added to magnesium (2.9 g, 0.12 mol) in tetrahydrofuran (20 ml) and the mixture stirred for one hour at room temperature. The solution formed was slowly added to a solution of 1-acetyl-4-piperidone (16.9 g, 0.12 mol) in tetrahydrofuran (200 ml) at -78° C., and the suspension produced was stirred to room temperature for 2 hours. Hydrochloric acid (120 ml, 1M) was added and the organic phase was separated and concentrated in vacuo. The residue was taken up in dichloromethane (300 ml), washed with water (300 ml) and dried (MgSO4). Concentration in vacuo and trituration with diethyl ether gave 1-[4-hydroxy-4-(4-methoxyphenyl)-piperidin-1-yl]ethanone (14.75 g, 50% yield) as a white solid; δH (CDCl3) 1.7-2.1 (4H, m, 2× piperidinyl CH2), 2.1 (3H, s, COCH3), 3.1 (1H, m, piperidinyl H), 3.6-3.8 (3H, m, piperidinyl H), 3.8 (3H, s, ArOCH3), 4.6 (1H, m, OH), 6.9 (2H, d, J 10 Hz, ArH), and 7.4 (2H, d, J 10 Hz, ArH).
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