tert-Butyl piperazine-1-carboxylate → tert-butyl 4-[2-fluoro-5-(trifluoromethyl)phenyl]piperazine-1-carboxylate

온도

105 °C

A 250 mL round flask was charged with 2-bromo-1-fluoro-4-(trifluoromethyl)benzene (1.016 g, 4.18 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.260 g, 0.42 mmol), Sodium tert-butoxide (0.482 g, 5.02 mmol), tert-butyl piperazine-1-carboxylate (0.779 g, 4.18 mmol) and a mixture of toluene (25 mL) and DMF (5 mL). The reaction mixture was degassed for 10 minutes with nitrogen, and then Tris(dibenzylideneacetone)dipalladium(0) (0.191 g, 0.21 mmol) was added. The reaction mixture was stirred at 105°C in an oil bath 12h. The solution was diluted with EtOAc and washed with saturated NaHCO3 solution, brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The aqueous phase was evaporated and the residue was extracted with EtOAc (3X20mL), concentrated. The combined crude material was loaded on a 80g silica gel column and purified on a Teledyne Isco instrument, eluting with 0% to 25% ethyl acetate in heptane to provide tert-butyl 4-(2-fluoro-5-(trifluoromethyl)phenyl)piperazine-1-carboxylate (0.622 g, 42.7 %) as an oil.

ORD 기록

ord-370c3c2e243949c9a11cec4ffc24deb1

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750 AstraZeneca ELN dataset

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