tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-[2-[(4-methylsulfonylphenyl)methoxy]pyrimidin-5-yl]piperazine-1-carboxylate

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5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyrimidine (748.8 mg, 2.18 mmol), tert- butyl piperazine-1-carboxylate (447 mg, 2.40 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (100 mg, 0.11 mmol),2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (67.9 mg, 0.11 mmol) and sodium 2-methylpropan-2-olate (315 mg, 3.27 mmol) were mixed with toluene (20 mL). N2 was bubbled through the solvent for 15 minutes.The resulting mixture was stirred at 80 °C for over night under N2.The reaction mixture was filtered through celite. The reaction mixture was evaporated to dryness and redissolved in EtOAc (75 mL), and washed sequentially with water (2x75 mL) and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-(4-(methylsulfonyl)benzyloxy)pyrimidin-5-yl)piperazine-1-carboxylate (55.0 %) as a yellow solid. Was not pure and tailed on the coloumn. The crude product was purified by preparative HPLC (Phenomenex Gemini C18 110A (axia) column, 5µ silica, 21 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.5% NH3 and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford as a white solid. The product crashed out on the HPLC coloumn and blocked the system, which gave bad recovery. Turns out the product is not stable. 2D TLC shows tailing of product..

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