2,2,2-Trifluoroethanol → 3-Chloro-2,5,6-trifluoro-4-(2,2,2-trifluoroethoxy)pyridine

온도

-78 °C

3-Chloro-2,4,5,6-tetrafluoropyridine (18.0 g, 97.0 mmol) was dissolved in anhydrous THF (100 mL) under an N2 atmosphere and the resulting solution cooled to −78° C. To the cold solution was slowly added a solution of sodium 2,2,2-trifluoroethoxide (97 mmol), prepared from trifluoroethanol (7.1 mL, 97.0 mmol) and NaH (3.88 g, 97.0 mmol, 60% dispersion in mineral oil), in anhydrous THF (100 mL). The resulting mixture was slowly warmed to ambient temperature. After 18 h at ambient temperature a GC analysis indicates all the starting material was consumed. The volatiles were evaporated and the residue dissolved in CH2Cl2 (200 mL). The organics were washed with H2O (3×100 mL), dried (MgSO4), filtered and concentrated to give the crude product as a yellow oil. The yellow oil was distilled at reduced pressure to afford 3-chloro-2,5,6-trifluoro-4-(2,2,2-trifluoroethoxy)pyridine as a clear oil (16.3 g, 63% yield): by 48° C. (ca 0.2 mm Hg); 1H NMR (CDCl3) δ 4.81-4.78 (dq, J=1.6, 7.7 Hz); GC-MS (EI, 70 eV) m/z (% relative intensity) 267 (33), 265 (100), 248 (5), 246 (16), 198 (22), 196 (60).

1. temperatureThe resulting mixture was slowly warmed to ambient temperature
2. customall the starting material was consumed
3. customThe volatiles were evaporated
4. dissolutionthe residue dissolved in CH2Cl2 (200 mL)
5. washThe organics were washed with H2O (3×100 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto give the crude product as a yellow oil
10. distillationThe yellow oil was distilled at reduced pressure

ORD 기록

ord-36fe99c487004500bbe6272f2fdde8e4

출처 데이터셋

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08507671B2