反应详情

4-Benzyloxy-2-pyridone (311.4 g, 1.55 mol) was mechanically stirred under nitrogen in a mixture of dioxane (6.2 L) and 50% sodium hydroxide (2.48 L) while chlorodifluoromethane (1,332.4 g, 15.5 mol) was condensed into the 22 L flask over a 4 h period using a dry-ice condenser that was attached to one of the necks of the 4-neck flask. The temperature inside the flask was maintained below 35° C. by means of an ice-bath. The mixture was then stirred for 18 h maintaining the temperature of the mixture between 25° C. and 35° C. The dry-ice condenser was in place during the 18 h reaction time. The mixture was then diluted with water, acidified to pH 1 with conc. HCl and extracted three times with ethyl acetate. If emulsions formed the whole mixture was filtered through a bed of celite. The combined organic layers were dried (MgSO4), filtered through silica gel and concentrated in-vacuo. The crude oil was chromatographed on a Prep-500 HPLC to give 2-difluoromethoxy-4-benzyloxypyridine (219.75 g, 56% yield) as a yellow oil, nD =1.5274. Anal. Calcd. for C13H11NO2F2 : C,62.15; H,4.41; N,5.58 Found: C,62.18; H,4.40; N,5.52.

1. customcondensed into the 22 L flask over a 4 h period
2. temperatureThe temperature inside the flask was maintained below 35° C. by means of an ice-bath
3. temperaturemaintaining the temperature of the mixture between 25° C. and 35° C
4. extractionextracted three times with ethyl acetate
5. customIf emulsions formed the whole mixture
6. filtrationwas filtered through a bed of celite
7. dry with materialThe combined organic layers were dried (MgSO4)
8. filtrationfiltered through silica gel
9. concentrationconcentrated in-vacuo
10. customThe crude oil was chromatographed on a Prep-500 HPLC