Citric Acid → HCID 89649116, compound

Participants

Reaction Steps

To an ice cooled solution of trifluoromethanesulfonic anhydride (0.29 mL, 1.72 mmol) in DCM (10 mL) was added 2-fluoro-5-(3-methylpyrazol-1-yl)phenol (which may be prepared as described in Description 68) (288 mg, 1.5 mmol) followed by pyridine (0.6 mL, 7.49 mmol). The reaction was stirred at 00° C. for 10 minutes, then allowed to warm to room temperature over 1 hour, then the reaction was stirred overnight at room temperature. Additional trifluoromethanesulfonic anhydride (0.29 mL, 1.72 mmol) was added and the reaction was stirred at room temperature for 1 hour. The reaction was diluted with DCM (30 mL) and subsequently poured into an aqueous solution of citric acid (10% w/w, 50 mL), and the layers were separated. The aqueous was then re-extracted with DCM (30 mL). The combined organics were dried through a phase separator, and concentrated in vacuo. The residue was loaded onto a silica column (10 g, SNAP cartidge), which was eluted with a gradient of EtOAc:isohexane, 0% to 30%. Fractions containing desired product were combined and concentrated in vacuo, to give [2-fluoro-5-(3-methylpyrazol-1-yl)phenyl]trifluoromethanesulfonate (D69) (308 mg, 0.9024 mmol, 60.2% yield);

Provenance & Evidence