Hydrogen Peroxide → HCID 67435388, compound

A solution of 3-fluoro-4-(trifluoromethyl)pyridine (5.00 g; 30.3 mmol) in CH2Cl2 (10 mL) was cooled to 0° C., then methyltrioxorhenium(VII) (0.062 g; 0.249 mmol) and hydrogen peroxide (30%; 6.2 mL; 61 mmol) were added and the mixture was warmed to room temperature. After stirring for 2 hours, the reaction was quenched by the addition of MnO2 (5 mg) and 30 minutes additional stirring. After dilution with additional CH2Cl2, the mixture was filtered through Solka Floe, dried (MgSO4) and concentrated in vacuo to provide 3-fluoro-4-(trifluoromethyl)pyridine 1-oxide of sufficient purity to be used directly. The N-oxide (3.70 g; 20.4 mmol) was dissolved in trifluoroacetic anhydride (21.6 mL; 153 mmol) in a hydrogenation bomb and heated to 85° C. for 15 hours. After cooling to 0° C., water was added, followed by solid K2CO3 until pH 9. The aqueous fraction was extracted with EtOAc and Me-THF, and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification by ISCO CombiFlash (70:30 to 0:100 hexanes:EtOAc) provided the title compound as a pink solid. 1H NMR (400 MHz, Acetone): δ 11.48 (s, 1 H); 7.55 (d, J=7.1 Hz, 1 H); 6.39 (t, J=6.2 Hz, 1 H).

1. customthe reaction was quenched by the addition of MnO2 (5 mg) and 30 minutes additional stirring
2. filtrationAfter dilution with additional CH2Cl2, the mixture was filtered through Solka Floe
3. dry with materialdried (MgSO4)
4. concentrationconcentrated in vacuo

ORD record

ord-47683afe911246848bac46cd7c17b353

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486975B2