Brc1ccc(I)cc1.C[C@@H]1CNC[C@H](C)N1>C1COCCO1.CC(=O)O.CC(=O)O.CC(C)(C)[O-].CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.[Na+].[Pd]>C[C@@H]1CN(c2ccc(Br)cc2)C[C@H](C)N1sodium 2-methylpropan-2-olate (4.08 g, 42.42 mmol) was added to (2R,6S)-2,6-dimethylpiperazine (4.84 g, 42.42 mmol) in dioxane (300 mL) at 21°C under nitrogen. Stirred for 5 mins. 1-bromo-4-iodobenzene (8 g, 28.28 mmol) added, followed by diacetoxypalladium (0.635 g, 2.83 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.27 g, 5.66 mmol). Reaction evacuated and refilled with nitrogen several times. Heated at 90C for 18hours. Diluted with ethyl acetate and filtered through celite. The organic layer was washed with water ( 500ml) and then dried over Na2SO4, filtered and reduced in volume. Filtered - lcms messy. Dissolved in DCM and combined with the filtrate - adsorbed onto silica. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford (3S,5R)-1-(4-bromophenyl)-3,5-dimethylpiperazine (4.69 g, 61.6 %) as a yellow solid.
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