Citric Acid → HCID 89649116, compound

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);

1. stirringthe reaction was stirred overnight at room temperature
2. stirringthe reaction was stirred at room temperature for 1 hour
3. customthe layers were separated
4. extractionThe aqueous was then re-extracted with DCM (30 mL)
5. customThe combined organics were dried through a phase separator
6. concentrationconcentrated in vacuo
7. washwas eluted with a gradient of EtOAc
8. additionFractions containing desired product
9. concentrationconcentrated in vacuo

ORD record

ord-690a5128f6d944988ba50fd9f1673eb6

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376436B2