Diisopropylethylamine → 7-Fluoro-5-methyl-3-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-benzoxazol-2(3H)-one hydrochloride

Participants

Reaction Conditions

Reaction Steps

DIPEA (0.14 mL, 0.79 mmol) was added to a solution of 2-fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol (D17, 51 mg, 0.16 mmol) in DCM (5 mL) at room temperature under argon. The reaction was cooled to 0° C. and the triphosgene (19 mg, 0.07 mmol) was added. The mixture was stirred for 30 min at 0° C., followed by a further 15 min at room temperature. 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 the crude product, which 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 white solid. The free base was dissolved in DCM (2 mL) at 25° C. HCl (0.24 mL, 0.24 mmol, 1 M in Et2O) was then added and the reaction was stirred for 15 min. The solvent was removed by rotary evaporation to give 7-fluoro-5-methyl-3-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-benzoxazol-2(3H)-one hydrochloride (E4, 47 mg, 70%) as a white solid.

Provenance & Evidence