反应详情

温度

0 °C

Hünig's base (0.07 mL, 0.401 mmol) was added to a solution of 5-fluoro-4-methyl-2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol (D5, 47 mg, 0.146 mmol) in dichloromethane (5 mL) at rt under argon. The reaction was cooled to 0° C., the triphosgene (22.8 mg, 0.077 mmol) was added and the mixture was stirred for 1 h at 0° C. The reaction was quenched with saturated aqueous NaHCO3 (5 mL) and partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane (2×) and the combined organics were dried (Na2SO4) and concentrated by rotary evaporation to give a brown oil. The crude residue was purified via chromatography (amino-doped silica, iso-hexane-ethyl acetate) to give the free base of the title compound as a white solid. HCl (0.05 mL, 0.05 mmol, 1 M in diethyl ether) was added to a solution of the free base in dichloromethane (0.5 mL). The solvent was removed by rotary evaporation and the resulting residue was triturated with diethyl ether (2×) to give 6-fluoro-5-methyl-3-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-benzoxazol-2(3H)-one hydrochloride (E1, 13.1 mg, 22% yield) as a white solid.

1. customThe reaction was quenched with saturated aqueous NaHCO3 (5 mL)
2. custompartitioned between dichloromethane and water
3. extractionThe aqueous layer was extracted with dichloromethane (2×)
4. dry with materialthe combined organics were dried (Na2SO4)
5. concentrationconcentrated by rotary evaporation
6. customto give a brown oil
7. customThe crude residue was purified via chromatography (amino-doped silica, iso-hexane-ethyl acetate)