2-Morpholinoethanol → {1-[4-Cyano-3-fluoro-5-(2-morpholin-4-yl-ethoxy)-phenyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

関与物質

反応条件

反応手順

To a solution of 0.10 g (0.30 mmol) of [1-(4-cyano-3,5-difluoro-phenyl)-piperidin-4-yl]-carbamic acid tert-butyl ester and 0.040 mL (0.33 mmol) of 4-(2-hydroxyethyl)-morpholine in THF (15 mL), cooled to 0° C., was added 0.60 mL (0.60 mmol) of sodium bis(trimethylsilyl)amide as a 1.0 M solution in THF. The reaction was stirred at 0° C. for 30 min then warmed to 60° C. for 6 h. The reaction was cooled to room temperature and excess base was consumed by the addition of a saturated aqueous solution of NH4Cl. The mixture was diluted with H2O and washed with EtOAc. The combined organic phase was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash silica gel chromatography to provide 0.081 g (61%) of {1-[4-cyano-3-fluoro-5-(2-morpholin-4-yl-ethoxy)-phenyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as a white foam.

情報源と証拠