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

Participants

Reaction Conditions

Reaction Steps

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

Provenance & Evidence