反应详情

温度

0 °C

DIPEA (0.1 mL, 0.57 mmol) was added to a solution of 2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}-4-(trifluoromethyl)phenol (D14, 89 mg, 0.25 mmol) in DCM (5 mL) at rt under Ar. The reaction was cooled to 0° C. and the triphosgene (31 mg, 0.10 mmol) was added. The mixture was stirred for 3 h at 0° C. The reaction was quenched with sat. NaHCO3 (5 mL) and partitioned between DCM and H2O. The aqueous layer was extracted with DCM (2×) and the combined organics were dried (Na2SO4) and concentrated by rotary evaporation to give a pale yellow solid. The residue was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM) to give the free base of the title compound as a colourless oil. HCl (0.5 mL, 0.5 mmol, 1 M in Et2O) was added to a solution of the free base in DCM (5 mL) and the reaction stirred for 30 min. The solvent was removed by rotary evaporation and the resulting solid triturated with Et2O to give 3-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-benzoxazol-2(3H)-one hydrochloride (E3, 81 mg, 73%) as a white solid.

1. customThe reaction was quenched with sat. NaHCO3 (5 mL)
2. custompartitioned between DCM and H2O
3. extractionThe aqueous layer was extracted with DCM (2×)
4. dry with materialthe combined organics were dried (Na2SO4)
5. concentrationconcentrated by rotary evaporation
6. customto give a pale yellow solid
7. customThe residue was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM)