methyl 4-bromo-2-[(2-methylpropan-2-yl)oxycarbonylamino]benzoate

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Nitrogen was bubbled into a mixture of methyl 4-bromo-2-(tert-butoxycarbonylamino)benzoate (0.62 g, 1.878 mmol), tert-butyl piperazine-1-carboxylate (0.350 g, 1.878 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.045 g, 0.094 mmol) and cesium carbonate (1.835 g, 5.63 mmol) in toluene (4 mL) for 10 min., followed by the addition of diacetoxypalladium (0.013 g, 0.056 mmol). The reaction mixture was stirred at 110° C. for two hours. The reaction mixture was cooled to RT. Water and ethyl acetate (30 mL/30 mL) were added. The two layers were separated in a separatory funnel The aqueous layer was extracted one more time with 30 mL of ethyl acetate. The product was purified by flash chromatography (1% EtOAc/DCM, Rf 0.44) to give 0.56 g (69% yield) of tert-Butyl 4-(3-(tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate. 1H-NMR (CDCl3, 400 MHz): δ 10.48 (1H, s), 8.01 (1H, d, J=2.5 Hz), 7.87 (1H, d, J=9.0 Hz), 6.46 (1H, dd, J1=9.0 Hz, J2=2.5 Hz), 3.86 (3H, s), 3.57 (4H, t, J=5.0 Hz), 3.36 (4H, t, J=5.0 Hz), 1.53 (9H, s), 1.49 (9H, s). The reaction mixture was cooled to RT The two layers were separated in a separatory funnel The aqueous layer was extracted one more time with 30 mL of ethyl acetate The product was purified by flash chromatography (1% EtOAc/DCM, Rf 0.44)