Trifluoroacetic acid → HCID 178520640, compound

Participants

Reaction Steps

(Trans-4-{3-oxo-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propyl}-cyclohexyl)-carbamic acid tert-butyl ester (23 mg, 0.06 mmol, prepared in accordance with Example 40) was combined with a 50% (vol/vol) solution of trifluoroacetic acid and dichloromethane (3 mL). The resulting mixture was stirred for 30 min at room temperature. The mixture was then concentrated under vacuum to form a crude residue. The crude residue was dissolved in dimethylsulfoxide (3 mL). Afterward, potassium carbonate was added (17 mg, 0.12 mmol). 5-Fluoro-2-nitrobenzotrifluoride (15 mg, 0.07 mmol) was then added. The resulting mixture was reacted at 120° C. for 18 hr. The mixture was then cooled to room temperature, diluted with dichloromethane (15 mL), washed with water (4×8 mL), washed with saturated aqueous ammonium chloride (8 mL), washed with water (8 mL), washed with saturated aqueous hydrogencarbonate (2×8 mL), and washed with water (2×8 mL). The organic phase was collected, dried over magnesium sulfate, and concentrated under vacuum to form a crude residue. The crude residue was purified by preparative HPLC. Following lyophilization of the fractions of interest, the desired product was isolated as a solid (17 mg, 48% yield). The structure was confirmed using Protocol I-A. Calculated mass=573; observed mass=553; HPLC retention time=4.98 min. It is believed that the discrepancy between the actual and observed masses stems from a loss of HF upon ionization.

Provenance & Evidence