Hydrochloric Acid → Ethyl(3-chloro-2,5,6-trifluoro-4-pyridinyl)acetate

Temperatur

-78 °C

To a solution of 11.8 mL (58 mmol) ethyl trimethylsilylmalonate in 150 mL THF at −78° C. was added 23 mL (58 mmol, 2.5M solution in hexane)butyllithium via syringe. The reaction mixture was stirred 15 min at −78° C. then warmed to 0° C. whereupon 5.1 g (27 mmol) 3-chloro-2,4,5,6-tetrafluoropyridine was added rapidly via syringe. Stir 1 hr at 0° C. then warmed to room temperature and stirred 16 hours. The reaction mixture was diluted with 400 mL ether, mixed vigorously with 300 mL 0.05M HCl for 5 min then brought to pH 4-5 w NaOH. The layers were separated and the ether layer was washed with 300 mL brine, dried over MgSO4, filtered, concentrated. Purification by automated flash chromatography (90 g silica cartridge, linear gradient 0-10% EtOAc/hex over 30 min, 70 mL/min flow rate.) afforded ethyl(3-chloro-2,5,6-trifluoro-4-pyridinyl)acetate 1-1 as a clear oil. 1H NMR (400 mHz, CDCl3) δ4.22 (q, 2H, J=7.33 Hz); 3.93 (d, 2H, J=1.95Hz); 1.29 (t, 3H, J=7.33 Hz). Mass Spec (electrospray) M+H=254.1

1. additionwas added rapidly via syringe
2. stirringStir 1 hr at 0° C.
3. temperaturethen warmed to room temperature
4. stirringstirred 16 hours
5. customThe layers were separated
6. washthe ether layer was washed with 300 mL brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by automated flash chromatography (90 g silica cartridge, linear gradient 0-10% EtOAc/hex over 30 min, 70 mL/min flow rate.)

ORD-Eintrag

ord-65ca6206654942de9fd2397b74b800c0

Quelldatensatz

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06610701B2