Water → 2-Chloro-3-(difluoromethoxy)pyridine

Temperatur

100 °C

As shown in step 3-i of Scheme 3, 2-chloro-3-hydroxypyridine (Compound 1005, 2.0 g, 15.4 mmol, obtained from Aldrich Chemical Co.) was dissolved in 40 mL of DMF and 5.0 mL of water along with sodium chlorodifluoroacetate (4.71 g, 30.9 mmol, obtained from Lancaster Synthesis, Inc.) and anhydrous potassium carbonate (2.56 g; 18.5 mmol). The reaction mixture was heated in an oil bath at 100° C. for 2 hours. Another equivalent of sodium chlorodifluoroacetate and 1.2 equiv. of potassium carbonate were added and heating continued for an additional 2.0 hours. After this time, the reaction was cooled and the volatiles removed under reduced pressure. The residue was partitioned between brine and ethyl acetate and the organics washed once more with brine, dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The product was purified by silica gel chromatography, eluting with a hexanes/DCM to DCM gradient, to produce 2-chloro-3-(difluoromethoxy)pyridine as a white solid (Compound 1006, 2.0 g, 72% yield): ESMS (M+H) 180; 1H NMR (CDCl3) δ 8.05 (m, 1H), 7.45 (m, 1H), 6.90 (m, 1H), 6.60 (t, 1H; J=75 Hz), 4.01 (s, 3H).

1. temperatureheating
2. temperatureAfter this time, the reaction was cooled
3. customthe volatiles removed under reduced pressure
4. customThe residue was partitioned between brine and ethyl acetate
5. washthe organics washed once more with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customthe volatiles removed under reduced pressure
9. customThe product was purified by silica gel chromatography
10. washeluting with a hexanes/DCM to DCM gradient

ORD-Eintrag

ord-b8cb72cfa3f0491da53c6819ec04d1df

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08524906B2