반응 #67630

반응 방정식

sodium chlorodifluoroacetate

Compound 1005

2-chloro-3-hydroxypyridine

water

potassium carbonate

2-chloro-3-hydroxypyridine

sodium chlorodifluoroacetate

potassium carbonate

→

2-chloro-3-(difluoromethoxy)pyridine

수율 72.0%

용매

DMF

반응 조건

후처리

1. 1
   온도heating
2. 2
   온도After this time, the reaction was cooled
3. 3
   기타the volatiles removed under reduced pressure
4. 4
   기타The residue was partitioned between brine and ethyl acetate
5. 5
   세척the organics washed once more with brine
6. 6
   건조dried over Na2SO4
7. 7
   여과filtered
8. 8
   기타the volatiles removed under reduced pressure
9. 9
   기타The product was purified by silica gel chromatography
10. 10
    세척eluting with a hexanes/DCM to DCM gradient

실험 절차

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).

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