[Mg].II.Br[C:5]1[CH:10]=[CH:9]C=[CH:7][CH:6]=1.[CH2:11]([N:18]1[CH2:23][CH2:22][C:21]([N:26]([CH3:28])[CH3:27])([C:24]#N)[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH4+].[Cl-]>C(OCC)C.CO.C(Cl)(Cl)Cl>[CH2:11]([N:18]1[CH2:19][CH2:20][C:21]([C:24]2[CH:9]=[CH:10][CH:5]=[CH:6][CH:7]=2)([N:26]([CH3:27])[CH3:28])[CH2:22][CH2:23]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
To a mixture of 34.5 g (3.5 equiv.) of magnesium and 100 ml of dry diethyl ether there were added first a small amount of iodine and then, over a period of 10 minutes, 10 g (0.15 equiv.) of bromobenzene, and stirring was carried out for a further 10 minutes. When the reaction had started, 183 g (2.85 equiv.) of bromobenzene dissolved in 500 ml of diethyl ether were added dropwise over a period of 2 hours, and stirring was continued for 15 minutes. 100 g (1 equiv.) of 1-benzyl-4-(dimethylamino)piperidine-4-carbonitrile dissolved in 900 ml of diethyl ether were added over a period of 2 hours to the Grignard reagent prepared above, and finally the mixture was heated for 12 hours at 80° C. The progress of the reaction was monitored by thin-layer chromatography (10% MeOH/CHCl3). When the reaction was complete, the reaction solution was cooled to 0° C.; saturated NH4Cl solution was added, the mixture was extracted with ethyl acetate (3×300 ml) and the combined organic phases were dried with Na2SO4. After removal of the solvent under reduced pressure, purification was carried out by column chromatography (silica gel; 1% MeOH/CHCl3). 30 g (35%) of product were obtained in the form of a yellow solid.
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