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

温度

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レコード

ord-370c3c2e243949c9a11cec4ffc24deb1

出典データセット

750 AstraZeneca ELN dataset

元リンク

出典を表示