2-Chloro-6-(difluoromethoxy)pyridine

To a vigorously stirred solution of 2-chloro-6-hydroxypyridine(0.13 g, 1.0 mmol) in acetonitrile (2 mL) at room temperature was added a 6 M aqueous solution of potassium hydroxide (2 mL). Difluoromethyltriflate (0.38 mL, 3.0 mmol, 3 equiv.) was added dropwiseto the reaction mixture which was maintained at room temperature by means of a water bath (the reaction is exothermic), and the medium was stirred for 30 min. The mixture was diluted with water(20 mL) and extracted with diethyl ether (2 ×10 mL) and ethyl acetate(3 ×10 mL). The combined organic layers were dried over Na2SO4, filtered and evaporated under reduced pressure. The crude material was purified by column chromatography on silica gel with pentane/diethylether (100:0 to 70:30) as eluent to afford the pure title compound(129 mg, 72percent yield); 1H NMR (400 MHz, CDCl3): δ 7.62 (t, 1H, J = 7.9 Hz), 7.37 (t, 1H, J = 72.2 Hz), 7.07 (d, 1H, J = 7.9 Hz), 6.76(d, 1H, J = 8.0 Hz) ppm. 13C NMR (101 MHz, CDCl3): δ 158.3, 148.5, 142.1, 120.1, 113.8 (t, J= 259 Hz), 109.6 ppm 19F NMR (376 MHz, CDCl3): δ −89.3 (d, 2F, J = 71.4 Hz) ppm. HRMS (ESI) calcd forC6H5ClF2NO [M + H]+: 180.002. Found: 180.000.General procedure: Using an apparatus previously described for method B solution of 6-chloropyridin-2-ol (1.0 equiv.), sodium 2-chloro-2, 2-difluoroacetate (2.0 equiv.) and sodium hydroxide (1.1 equiv.) in DMF (0.77 M) was heated at 55° C. for 18 hrs, the reaction mixture was then partitioned between EtOAc and sat. NaHCO

Molecular Weight:179.55
XLogP3:3.1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:178.9949478
Monoisotopic Mass:178.9949478
Topological Polar Surface Area:22.1
Heavy Atom Count:11
Complexity:125
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes