To a solution of 4,16-dibromo[2,2]paracyclophane (2.90 g, 7.92 mmol, 1.00 equiv.) in toluene (100.0 mL) was added benzophenone imine (1.51 g, 8.32 mmol, 1.05 equiv.), Pd(dppf)2Cl2 (323 mg, 0.396 mmol, 0.05 equiv.), DPPF (869 mg, 1.19 mmol, 0.15 equiv.), and sodium t-butoxide (2.28 g, 23.76 mmol, 3.00 equiv.). The mixture was stirred at 100 °C under argon for 16 hours. After the reaction mixture was cooled to 21 °C, diluted with CH2Cl2 (100.0 mL), acetic acid was added to the mixture until the stirred solution tested acidic (pH 6), washed with water (3 × 50 mL), saturated aqueous NaCl solution (3 × 50 mL) and dried over magnesium sulfate. The solvent was removed under reduced pressure to give a residue. The intermediate product was directly used as a crude for the following reaction.To a solution of crude product in THF (35.0 mL) was added concentrated HCl (2.5 mL), and stirred at 21 °C for 4h. After the yellow mixture faded, the white precipitate formed was filtered, washed with ether (3 × 5.0 mL), and dried in vacuo. The remaining solid in ethanol (4.0 mL) was stirred, and saturated NaOH was added dropwise until the stirred mixture tested basic (pH 9). The crude product was purified via flash column chromatography on silica gel using DCM/MeOH 20:1, obtaining 4-bromo-16-anmino[2.2]paracyclophane (756 mg, 2.50 mmol, 32%) as a light brown solid.
