Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.O.[Pd]>[ClH:16].[Cl:16][C:17]1[CH:22]=[C:21]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[O:9])=[CH:4][CH:3]=2)[CH:20]=[CH:19][CH:18]=1
A round bottom flask was charged with (4-bromophenyl)(piperidine-4-yl)methanone (20.0 g, 74.6 mmol), 3-chlorophenyl boronic acid (17.4 g, 111 mmol, 1.5 eq), and palladium encapsulated catalyst (Aldrich, Pd EnCat-TPP®, catalyst species PdCl2(PPh3)2) (5.2 g, 0.187 mmol, 0.05 eq). These solids were suspended in isopropanol (570 ml) and allowed to stir for five minutes. To the mixture was added potassium carbonate (30.8 g, 224 mmol, 3 eq) dissolved in H2O (30 ml). The reaction mixture was heated to 80° C. for 16 hours and deemed complete by LC/MS. The suspension was filtered through a small bed of Celite® and the filtrate was concentrated to dryness. The resulting solids were dissolved in isopropyl acetate (400 ml) and washed with water (3×75 ml). The organic layer was then cooled to 0° C. (ice/water bath) and to this stirring solution was added slowly 6 N HCl until solids crystallized. The solids were filtered and dried in a vacuum oven for 16 hours at 50° C. to afford 16.9 g of compound 2 (68% yield) in >98% HPLC purity. MH+=300, 302 (about 3:1). Palladium: 3 ppm.
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