[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[C@H:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](F)[CH:20]=1>CN(C)C=O>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Br:18])[CH:20]=2)[C@H:10]([CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Dissolve 1-benzyl-cis-3-methyl-piperidin-4-ol (preparation 6, 3.84 g, 18.73 mmol) in dry N,N-dimethylformamide (100 mL), treat with 60% sodium hydride (1.05 g, 26.22 mmol), heat and stir at 80° C. After 1 hr., add-1-bromo-3-fluoro-benzene (2.51 mL, 22.45 mmol), stir and heat at 110° C. After 16 hr., cool to ambient temperature. Partition between water (100 mL) and ethyl acetate (100 mL), wash the aqueous layer with ethyl acetate (2×100 mL), combine the organic layers, wash with water (5×100 mL) and aqueous NaCl solution (100 mL). Dry the organic layer over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 2% (2M NH3/methanol)/methylene dichloride to obtain the title compound as a mixture of enantiomers (1.69 g, 24%). 1H NMR (CDCl3): 7.3 (m, 5H), 7.1 (m, 3H), 6.8 (m, 1H), 4.3 (m, 1H), 3.5 (d, 2H), 2.5 (m, 2H), 2.4 (m, 2H), 2.0 (m, 2H), 1.8 (m, 1H), 1.0 (d, 3H).
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