Trifluoroacetic anhydride → 2-Chloro-5-(trifluoromethyl)pyridine 1-oxide

Cool a DCM (500 mL) solution of 2-chloro-5-trifluoromethylpyridine (96 g, 529 mmol) to 0° C. in an ice bath. Add urea hydrogen peroxide (105 g, 1111 mmol), followed by dropwise addition of trifluoroacetic anhydride (147 mL, 1058 mmol), and allow the reaction mixture to reach room temperature. After 22 hours, TLC (50% EtOAc/Hexanes) shows only a trace amount of starting material. Quench the reaction with sat. aqueous Na2S2O3 and stir for 15 minutes to destroy any residual peroxides. Then, pour the mixture into 0.5 M HCl (300 mL) and extract with CH2Cl2 (2×200 mL). Wash the combined organic extracts with sat. NaHCO3 (3×100 mL), dry over Na2SO4, filter, and concentrate under vacuum to give the title product as a pale yellow solid, which is used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.64 (d, 1H, J=8.4 Hz), 7.38 (d, 1H, J=8.0 Hz). Mass spec. (481.11, M+H).

1. customto reach room temperature
2. customQuench
3. customthe reaction with sat. aqueous Na2S2O3
4. customto destroy any residual peroxides
5. additionThen, pour the mixture into 0.5 M HCl (300 mL)
6. extractionextract with CH2Cl2 (2×200 mL)
7. washWash the combined organic extracts with sat. NaHCO3 (3×100 mL)
8. dry with materialdry over Na2SO4
9. filtrationfilter
10. concentrationconcentrate under vacuum

ORD-Eintrag

ord-357fea5ad95142ca9c170521a7646c1d

Quelldatensatz

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07935702B2